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Patch-Clamp and Voltage-Clamp Techniques

  • Michael Gralinski
  • Liomar A. A. Neves
  • Olga Tiniakova
Reference work entry

Abstract

The introduction of the patch-clamp technique (Neher and Sakmann 1976) revolutionized the study of cellular physiology by providing a high-resolution method of observing the function of individual ionic channels in a variety of normal and pathological cell types. By the use of variations of the basic recording methodology, cellular function and regulation can be studied at a molecular level by observing currents through individual ionic channels (Liem et al. 1995; Sakmann and Neher 1995).

Keywords

Cystic Fibrosis Transmembrane Conductance Regulator Xenopus Oocyte Patch Pipette Tyrode Solution Borosilicate Glass Capillary 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References and Further Reading

Patch-Clamp Technique

  1. Asmild M, Oswald N, Krzywkowski FM, Friis S, Jacobsen RB, Reuter D, Taboryski R, Kutchinsky J, Vestergaard RK, Schroder RL, Sorensen CB, Bech M, Korsgaard MP, Willumsen NJ (2003) Upscaling and automation of electrophysiology: toward high throughput screening in ion channel drug discovery. Receptor Channels 9:49–58Google Scholar
  2. Bennett PB, Guthrie HRE (2003) Trends in ion channel drug discovery: advances in screening technologies. Trends Biotechnol 21:563–569PubMedGoogle Scholar
  3. Brueggemann A, George M, Klau M, Beckler M, Steimdl J, Behrends JC, Fertig N (2004) Ion channel drug discovery and research. The automated nano-patch-clamp technology. Curr Drug Discov Technol 1:91–96PubMedGoogle Scholar
  4. Brüggemann A, Stoelzle S, George M, Behrends JC, Fertig N (2006) Microchip technology for automated and parallel patch-clamp recording. Small 2:840–846PubMedGoogle Scholar
  5. Cavalié A, Grantyn R, Lux HD (1993) Fabrication of patch clamp pipettes. In: Kettenmann H, Grantyn R (eds) Practical electrophysiological methods. Wiley, New York, pp 235–240Google Scholar
  6. Dietzel ID, Bruns D, Polder HR, Lux HD (1993) Voltage clamp recording. In: Kettenmann H, Grantyn R (eds) Practical electrophysiological methods. Wiley, New York, pp 256–262Google Scholar
  7. Falconer M, Smith F, Surah-Narwal S, Congrave G, Liu Z, Hayter P, Ciaramella G, Keighley W, Haddock P, Waldron G, Sewing A (2002) High-throughput screening for ion channel modulators. J Biomol Screen 7:460–465PubMedGoogle Scholar
  8. Fertig N, Klau M, George M, Blick RH, Behrends JC (2002) Activity of single ion channel proteins detected with a planar microstructure. Appl Phys Lett 81:4865–4867Google Scholar
  9. Hamill OP (1993) Cell-free patch clamp. In: Kettenmann H, Grantyn R (eds) Practical electrophysiological methods. Wiley, New York, pp 284–288Google Scholar
  10. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100PubMedGoogle Scholar
  11. Jackson MB (1993) Cell-attached patch. In: Kettenmann H, Grantyn R (eds) Practical electrophysiological methods. Wiley, New York, pp 279–283Google Scholar
  12. Krzywkowski K, Schroder RL, Ljungstrom T, Kutchinsky J, Friis S, Vestergaard RK, Jacobsen RB, Pedersen S, Helix N, Sorensen CB, Bech M, Willumsen NJ (2004) Automation of the patch-clamp technique: technical validation through identification and characterization of potassium channel blockers. Biophys J 86:483aGoogle Scholar
  13. Kutchinsky J, Friis S, Asnild M, Taboryski R, Pedersen S, Vestergaard RK, Jacobsen RB, Krzywkowski K, Schroder RL, Ljungstrom T, Helix N, Sorensen CB, Bech M, Willumsen NJ (2003) Characterization of potassium channel modulators with QPatch automated patch-clamp technology system characteristics and performance. Assay Drug Dev Technol 1:685–693PubMedGoogle Scholar
  14. Liem LK, Simard JM, Song Y, Tewari K (1995) The patch clamp technique. Neurosurgery 36:382–392PubMedGoogle Scholar
  15. Mathes C (2003) Ion channels in drug discovery and development. Drug Discov Today 8:1022–1024PubMedGoogle Scholar
  16. Neher E, Sakmann B (1976) Single-channel currents recorded from membranes of denervated frog muscle fibres. Nature 260:799–802PubMedGoogle Scholar
  17. Sakmann B, Neher E (1995) Single-cell recording. Plenum, New YorkGoogle Scholar
  18. Schroeder K, Neagle B, Trezise DJ, Worley J (2003) Ion-Works™ HT: a new high-throughput electrophysiology measurement platform. J Biomol Screen 8:50–64PubMedGoogle Scholar
  19. Smith PA (1995) Methods for studying neurotransmitter transduction mechanisms. J Pharmacol Toxicol Methods 33:63–73PubMedGoogle Scholar
  20. Spencer CI, Li N, Chen Q, Johnson J, Nevill T, Kammonen J, Ionescu-Zanetti C (2012) Ion channel pharmacology under flow: automation via well-plate microfluidics. Assay Drug Dev Technol 10(4):313–324PubMedGoogle Scholar

Patch Clamp Technique in Isolated Cardiac Myocytes

  1. Anno T, Hondeghem LM (1990) Interactions of flecainide with guinea pig cardiac sodium channels. Circ Res 66:789–803PubMedGoogle Scholar
  2. Bennett PB, Stroobandt R, Kesteloot H, Hondeghem LM (1987) Sodium channel block by a potent, new antiarrhythmic agent, transcainide, in guinea pig ventricular myocytes. J Cardiovasc Pharmacol 9:661–667PubMedGoogle Scholar
  3. Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, Kühlkamp V (1999) Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 44:121–131PubMedGoogle Scholar
  4. Gögelein H, Hartung J, Englert HC, Schölkens BA (1998) HMR 1883, a novel cardioselective inhibitor of the ATP-sensitive potassium channel. Part I. Effects on cardiomyocytes, coronary flow and pancreatic β-cells. J Pharmacol Exp Ther 286:1453–1464PubMedGoogle Scholar
  5. Gwilt M, Dalrymple HW, Burges RA, Blackburn KJ, Dickinson RP, Cross PE, Higgins AJ (1991) Electrophysiologic properties of UK-66,914, a novel class III antiarrhythmic agent. J Cardiovasc Pharmacol 17:376–385PubMedGoogle Scholar
  6. Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch 391:85–100PubMedGoogle Scholar
  7. Monyer H, Lambolez B (1995) Molecular biology and physiology at the single-cell level. Curr Opin Neurobiol 5:382–387PubMedGoogle Scholar
  8. Neher E, Sakmann B (1976) Single-channel currents recorded from membranes of denervated frog muscle fibres. Nature 260:799–802PubMedGoogle Scholar
  9. Pallotta BS (1987) Patch-clamp studies of ion channels. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven, New York, pp 325–331Google Scholar
  10. Ryttsén F, Farre C, Brennan C, Weber SG, Nolkrantz K, Jardemark K, Chiu DT, Orwar O (2000) Characterization of single-cell electroporation by using patch-clamp and fluorescence microscopy. Biophys J 79:1993–2001PubMedCentralPubMedGoogle Scholar
  11. Terzic A, Jahangir A, Kurachi Y (1994) HOE-234, a second generation K+ channel opener, antagonizes the ATP-dependent gating of cardiac ATP-sensitive K+ channels. J Pharmacol Exp Ther 268:818–825PubMedGoogle Scholar
  12. Tsien RW, Lipscombe D, Madison DV, Bley RK, Fox AP (1988) Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci 11:431–438PubMedGoogle Scholar
  13. Yazawa K, Kaibara M, Ohara M, Kameyama M (1990) An improved method for isolating cardiac myocytes useful for patch-clamp studies. Jpn J Physiol 40:157–163PubMedGoogle Scholar

Voltage Clamp Studies on Sodium Channels

  1. Abriel H, Wehrens XHT, Benhorin J, Kerem B, Kass RS (2000) Molecular pharmacology of the sodium channel mutation DI790G linked to the long-QT- syndrome. Circulation 102:921–925PubMedGoogle Scholar
  2. Bezanilla F, Armstrong CM (1977) Inactivation of the sodium channel: I. Sodium current experiments. J Gen Physiol 70:549–566PubMedCentralPubMedGoogle Scholar
  3. Busch AE, Suessbrich H, Kunzelmann K, Hipper A, Greger R, Waldegger S, Mutschler E, Lindemann B, Lang F (1995) Blockade of epithelial Na+ channels by triamterenes – underlying mechanisms and molecular basis. Pflugers Arch 432:760–766Google Scholar
  4. Canessa CM, Schild L, Buell G, Thorens B, Gautschi I, Horisberger JD, Rossier BC (1994) Amiloride-sensitive N+ channel is made of three homologous subunits. Nature 367:463–467PubMedGoogle Scholar
  5. Catterall WA (1986) Molecular properties of voltage-sensitive sodium channels. Annu Rev Biochem 55:953–985PubMedGoogle Scholar
  6. Eller P, Berjukov S, Wanner S, Huber I, Hering S, Knaus HG, Toth G, Kimball SD, Striessnig J (2000) High affinity interaction of mibefradil with voltage-gated calcium and sodium channels. Br J Pharmacol 130:669–677PubMedCentralPubMedGoogle Scholar
  7. Endou H, Hosoyamada M (1995) Potassium-retaining diuretics: aldosterone antagonists. In: Greger RH, Knauf H, Mutschler E (eds) Handbook of experimental pharmacology, vol 117. Springer, Berlin/Heidelberg/New York, pp 335–362Google Scholar
  8. Erdõ SL, Molnár P, Lakics V, Bence JZ, Tömösközi Z (1996) Vincamine and vincanol are potent blockers of voltage-gated Na+ channels. Eur J Pharmacol 314:69–73PubMedGoogle Scholar
  9. Haeseler G, Leuwer M, Kavan J, Würz A, Dengler R, Piepenbrock S (1999) Voltage-dependent block of normal and mutant muscle sodium channels by 4-Chloro-m-Cresol. Br J Pharmacol 128:1259–1267PubMedCentralPubMedGoogle Scholar
  10. Khalifa M, Daleau P, Turgeon J (1999) Mechanism of sodium channel block by venlafaxine in guinea pig ventricular myocytes. J Pharmacol Exp Ther 291:280–284PubMedGoogle Scholar
  11. Makielski JC, Ye B, Valdivia CR, Pagel MD, Pu J, Tester DJ, Ackerman MJ (2003) A ubiquitous splice variant and a common polymorphisms affect heterologous expression of recombinant human SCN5AS heart sodium channels. Circ Res 93:821–828PubMedGoogle Scholar
  12. Nawada T, Tanaka Y, Hisatome I, Sasaki N, Ohtahara A, Kotake H, Mashiba H, Sato R (1995) Mechanism of inhibition of the sodium current by bepridil in guinea-pig isolated ventricular cells. Br J Pharmacol 116:1775–1780PubMedCentralPubMedGoogle Scholar
  13. Palmer LG (1992) Epithelial Na channels: function and diversity. Annu Rev Physiol 54:51–66PubMedGoogle Scholar
  14. Ragsdal DS, Numann R, Catterall WA, Scheuer T (1993) Inhibition of Na+ channels by the novel blocker PD85,639. Mol Pharmacol 43:949–954Google Scholar
  15. Song J-H, Jang Y-Y, Shin Y-K, Lee C-S, Chung S (2000) N-Ethyl-maleimide modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels in rat dorsal root neurons. Brain Res 855:267–273PubMedGoogle Scholar
  16. Sunami A, Hiraoka M (1996) Blockade of cardiac Na+ channels by a charged class I antiarrhythmic agent, bisaramil: possible interaction of the drug with a pre-open closed state. Eur J Pharmacol 312:245–255PubMedGoogle Scholar
  17. Taglialatela M, Ongini E, Brown AM, di Renzo G, Annunziato L (1996) Felbamate inhibits cloned voltage-dependent Na+ channels from human and rat brain. Eur J Pharmacol 316:373–377PubMedGoogle Scholar
  18. Viswanathan PV, Bezzina CR, George AL Jr, Roden DM, Wilde AAM, Balser JR (2001) Gating mechanisms for flecainide action in SNCN5A-linked arrhythmia syndromes. Circulation 104:1200–1205PubMedGoogle Scholar
  19. Wang DW, Yazawa K, Makita N, George AL Jr, Bennett PB (1997) Pharmacological targeting of long QT mutant sodium channels. J Clin Invest 99:1714–1720PubMedCentralPubMedGoogle Scholar

Voltage Clamp Studies on Potassium Channels

  1. Alexander S, Peters J, Mathie A, MacKenzie G, Smith A (2001) TiPS nomenclature supplement 2001Google Scholar
  2. Anson BD, Ackerman MJ, Tester DJ, Will ML, Delisle BP, Anderson CL, January CT (2004) Molecular and functional characterization of common polymorphism in HERG (KCNH2) potassium channels. Am J Physiol 286:H2434–H2441Google Scholar
  3. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G (1996) KvLQT1 and IsK (minK) proteins associate to form the IKs cardiac potassium current. Nature 384:78–80PubMedGoogle Scholar
  4. Bosch RF, Gaspo R, Busch AE, Lang HJ, Li R-G, Nattel S (1998) Effects of the chromanol 293B, a selective blocker of the slow component of the delayed rectifier K+ current, on repolarization in human and guinea pig ventricular myocytes. Cardiovasc Res 38:441–450PubMedGoogle Scholar
  5. Busch AE, Suessbrich H, Waldegger S, Sailer E, Greger R, Lang HJ, Lang F, Gibson KJ, Maylie JG (1996) Inhibition of I Ks in guinea pig cardiac myocytes and guinea pig I sK channels by the chromanol 293B. Pflugers Arch 432:1094–1096PubMedGoogle Scholar
  6. Cao Y-J, Dreixler JC, Roizen JD, Roberts MT, Houamed KM (2001) Modulation of recombinant small-conductance Ca2+ -activated K+ channels by the muscle relaxant chlorzoxazone and structurally related compounds. J Pharmacol Exp Ther 296:683–689PubMedGoogle Scholar
  7. Carmeliet A, Mubagawa K (1998) Antiarrhythmic drugs and cardiac ion channels: mechanism of action. Prog Biophys Mol Biol 70:1–71PubMedGoogle Scholar
  8. Chabbert C, Chambard JM, Sans A, Desmadryl G (2001) Three types of depolarization-activated potassium currents in acutely isolated mouse vestibular neurons. J Neurophysiol 85:1017–1026PubMedGoogle Scholar
  9. Champeroux P, Guth BD, Markert M, Rast G (2013) Methods in Cardiovascular Safety Pharmacology. In: Vogel HG, Maas J, Hock FJ, Mayer D (eds) Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays, 2nd edn. Springer Berlin Heidelberg. p. 73–97Google Scholar
  10. Colatsky TJ, Follmer CH, Starmer CF (1990) Channel specificity in antiarrhythmic drug action. Mechanism of potassium channel block and its role in suppressing and aggravating cardiac arrhythmias. Circulation 82:2235–2242PubMedGoogle Scholar
  11. Escande D, Henry P (1993) Potassium channels as pharmacological targets in cardiovascular medicine. Eur Heart J 14(Suppl B):2–9PubMedGoogle Scholar
  12. Gintant GA (1996) Two components of delayed rectifier current in canine atrium and ventricle. Does I Ks play a role in the reverse rate dependence of class III agents? Circ Res 78:26–37PubMedGoogle Scholar
  13. Gögelein H, Brüggemann A, Gerlach U, Brendel J, Busch AE (2000) Inhibition of I Ks channels by HMR 1556. Naunyn-Schmiedebergs Arch Pharmacol 362:480–488PubMedGoogle Scholar
  14. Golding AL (1992) Maintenance of Xenopus laevis and oocyte injection. Methods Enzymol 207:266–279Google Scholar
  15. Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, Chandy KG (1994) Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol 45:1227–1234PubMedGoogle Scholar
  16. Kaczorowski GJ, Garcia ML (1999) Pharmacology of voltage-gated and calcium-activates potassium channels. Curr Opin Chem Biol 3:448–458PubMedGoogle Scholar
  17. Lei M, Brown HF (1996) Two components of the delayed rectifier potassium current, IK, in rabbit sinoatrial node cells. Exp Physiol 81:725–741PubMedGoogle Scholar
  18. Longobardo M, Delpón E, Caballero R, Tamargo J, Valenzuela C (1998) Structural determinants of potency and stereoselective block of hKv1.5 channels induced by local anesthetics. Mol Pharmacol 54:162–169PubMedGoogle Scholar
  19. Methfessel C, Witzemann V, Takahashi T, Mishina M, Numa S, Sakmann B (1986) Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor. Pflugers Arch 407:577–588PubMedGoogle Scholar
  20. Moreno I, Caballero R, Ganzález T, Arias C, Valenzuela C, Iriepa I, Gálvez E, Tamargo J, Delpón E (2003) Effects of irbesartan on cloned potassium channels involved in human cardiac repolarization. J Pharmacol Exp Ther 304:862–873PubMedGoogle Scholar
  21. Sanchez-Chapula JA (1999) Mechanisms of transient outward K+ channel block by disopyramide. J Pharmacol Exp Ther 290:515–523PubMedGoogle Scholar
  22. Sanchez-Chapula JA, Navarro-Polanco RA, Culberson C, Chen J, Sanguinetti MC (2002) Molecular determinants of voltage-dependent human ether-a-go-go related gene (HERG) K+ channel block. J Biol Chem 277:23587–23595PubMedGoogle Scholar
  23. Sanguinetti MC, Jurkiewicz NK (1990) Two components of cardiac delayed rectifier K+ currents: differential sensitivity to block by class III antiarrhythmic agents. J Gen Physiol 96:195–215PubMedGoogle Scholar
  24. Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MD (1996) Coassembly of KvLTQ1 and minK (IsK) proteins form cardiac IKs potassium channel. Nature 384:80–83PubMedGoogle Scholar
  25. Suessbrich H, Busch A, Ecke D, Rizzo M, Waldegger S, Lang F, Szabo I, Lang HJ, Kunzelmann K, Greger R, Busch AE (1996) Specific blockade of slowly activating channels by chromanols – impact on the role of I sK channels in epithelia. FEBS Lett 396:271–275PubMedGoogle Scholar
  26. Suessbrich H, Busch AE, Scherz MW (1997) The pharmacology of cloned cardiac potassium channels. Ion Channel Modulators 2:432–439Google Scholar
  27. Tagliatela M, Timmerman H, Annunziato L (2000) Cardiotoxic potential and CNS effects of first-generation antihistamines. Trends Pharmacol Sci 21:52–65Google Scholar
  28. Vandenberg JI, Walker BD, Campbell TC (2001) HERG K+ channels: friend and foe. Trends Pharmacol Sci 22:240–246PubMedGoogle Scholar
  29. Wang Z, Fermini B, Nattel S (1994) Rapid and slow components of delayed rectifier current in human atrial myocytes. Cardiovasc Res 28:1540–1546PubMedGoogle Scholar
  30. Zhou J, Angelli-Szafran CE, Bradley JA, Chen X, Koci BJ, Volberg WA, Sun Z, Cordes JS (2005) Novel potent human Ether-à-Go-Go-related gene (hERG) potassium channel enhancers and their in vitro antiarrhythmic activity. Mol Pharmacol 68:876–884PubMedGoogle Scholar

Studies on Kv1.5 Channel

  1. Bachmann A, Gutcher I, Kopp K, Brendel J, Bosch RF, Busch AE, Gögelein H (2001) Characterization of a novel Kv1.5 channel blocker in Xenopus oocytes, CHO cells, and human cardiomyocytes. Naunyn-Schmiedebergs Arch Pharmacol 364:472–478PubMedGoogle Scholar
  2. Caballero R, Delpón E, Valenzuela C, Longobardo M, Tamargo J (2000) Losartan and its metabolite E3174 modify cardiac delayed rectifier K+ currents. Circulation 101:1199–1205PubMedGoogle Scholar
  3. Caballero R, Delpón E, Valenzuela C, Longobardo M, González T, Tamagro J (2001) Direct effects of candesartan and eprosartan in human cloned potassium channels involved in cardiac repolarization. Mol Pharmacol 59:825–836PubMedGoogle Scholar
  4. Caballero R, Gómez R, Núòez L, Moreno I, Tamargo J, Delpón E (2004) Diltiazem inhibits hKv1.5 and Kv4.3 currents in therapeutic concentrations. Cardiovasc Res 64:457–466PubMedGoogle Scholar
  5. Choe H, Lee YK, Lee YT, Choe H, Ko SH, Joo CU, Kim MH, Kim GS, Eun JS, Kim JH, Chae SW, Kwak YG (2003) Papaverine blocks hKv1.5 channel current and human atrial ultrarapid delayed rectifier K+ currents. J Pharmacol Exp Ther 304:706–712PubMedGoogle Scholar
  6. Choi BH, Choi JS, Rhie DJ, Yoon SH, Min DS, Jo YH, Kim MS, Hahn SJ (2002) Direct inhibition of the cloned Kv1.5 channel by AG-1478, a tyrosine kinase inhibitor. Am J Physiol 282:C1461–C1468Google Scholar
  7. Decher N, Uyguner O, Scherer CR, Karaman B, Yüksel-Apak M, Busch AE, Steinmeyer K, Wollnik B (2001) hKChIP2 is a functional modifier of hKv4.3 potassium channels: cloning and expression of a short hKChIP2 splice variant. Cardiovasc Res 52:255–264PubMedGoogle Scholar
  8. Dilks D, Ling H-P, Cockett M, Sokol P, Numann R (1999) Cloning and expression of the human Kv4.3 potassium channel. J Neurophysiol 81:1974–1977PubMedGoogle Scholar
  9. Fedida D, Eldstrom J, Hesketh C, Lamorgese M, Castel L, Steele DF, van Wagoner DR (2003) Kv1.5 is an important component of repolarizing K+ current in canine atrial myocytes. Circ Res 93:744–751PubMedGoogle Scholar
  10. Godreau D, Vranckx R, Hatem SN (2002) Mechanism of action of antiarrhythmic agent bertosamil on hKv1.5 channels and outward current in human atrial myocytes. J Pharmacol Exp Ther 300:612–620PubMedGoogle Scholar
  11. Godreau D, Vranckx R, Maguy A, Goyenvalle C, Hatem SN (2003) Different isoforms of synapse-associated protein, SAP97, are expressed in the heart and have distinct effects on the voltage-gated K+ channel Kv1.5. J Biol Chem 278:47046–47052PubMedGoogle Scholar
  12. Gögelein H, Hartung J, Englert HC, Schölkens BA (1998) HMR 1883, a novel cardioselective inhibitor of the ATP-sensitive potassium channel. I. Effects on cardiomyocytes, coronary flow and pancreatic β-cells. J Pharmacol Exp Ther 286:1453–1464PubMedGoogle Scholar
  13. Gögelein H, Brendel J, Steinmeyer K, Strübing C, Picard N, Rampe D, Kopp K, Busch AE, Bleich M (2004) Effects of the antiarrhythmic drug AVE0118 on cardiac ion channels. Naunyn-Schmiedebergs Arch Pharmacol 370:183–192PubMedGoogle Scholar
  14. Hamill OP, Marty M, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100PubMedGoogle Scholar
  15. Kobayashi S, Reien Y, Ogura T, Saito T, Masuda Y, Nakaya H (2001) Inhibitory effect of bepridil on hKv1.5 channel current; comparison with amiodarone and E-4031. Eur J Pharmacol 430:149–157PubMedGoogle Scholar
  16. Krause E, Englert H, Gögelein H (1995) Adenosine triphosphate-dependent K currents activated by metabolic inhibition in rat ventricular myocytes differ from those elicited by the channel opener rilmakalim. Pflugers Arch 429:625–635PubMedGoogle Scholar
  17. Li GR, Feng J, Wang Z, Fermine B, Nattel S (1996) Adrenergic modulation of ultrarapid rectifier K+ current in human atrial myocytes. Circ Res 78:903–915PubMedGoogle Scholar
  18. Longobardo M, González T, Navarro-Polanco R, Calballero R, Delpón E, Tamargo J, Snyders DJ, Tamkum MM, Valenzuela C (2000) Effects of a quaternary bupivacaine derivative on delayed rectifier K+ currents. Br J Pharmacol 130:391–401PubMedCentralPubMedGoogle Scholar
  19. Matsuda T, Masumiya H, Tanaka N, Yamashita T, Tsuruzoe N, Tanaka Y, Tanaka H, Shigenoba K (2001) Inhibition by a novel anti-arrhythmic agent, NIP-142, of cloned human cardiac K+ channel Kv1.5 current. Life Sci 68:2017–2024PubMedGoogle Scholar
  20. Moreno I, Caballero R, González T, Arias C, Valenzuela C, Iriepa I, Gálvez E, Tamargo J, Delpón E (2003) Effects of irbesartan on cloned potassium channels involved in human cardiac repolarization. J Pharmacol Exp Ther 304:862–873PubMedGoogle Scholar
  21. Perchenet L, Clément-Chomienne O (2000) Characterization of the mibefradil block of the human heart delayed rectifier hKv1.5. J Pharmacol Exp Ther 295:771–778PubMedGoogle Scholar
  22. Peukert S, Brendel J, Pirad B, Bruggemann A, Below P, Kleemann HW, Hemmerle H, Schmidt W (2003) Identification, synthesis, and activity of novel blockers of the voltage-gated potassium channel Kv1.5. J Med Chem 46:486–498PubMedGoogle Scholar
  23. Peukert S, Brendel J, Pirard B, Strübing C, Kleemann HW, Böhme T, Hemmerle H (2004) Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel. Bioorg Med Chem Lett 14:2823–2827PubMedGoogle Scholar
  24. Plane F, Johnson R, Kerr P, Wiehler W, Thorneloe K, Ishii K, Chen T, Cole W (2005) Heteromultimeric Kv1 channels contribute to myogenic control of arterial diameter. Circ Res 96:216–224PubMedGoogle Scholar
  25. Rampe D, Roy ML, Dennis A, Brown AM (1997) A mechanism for the proarrhythmic effects of cisapride (Propulsid): high affinity blockade of the human cardiac potassium channel HERG. FEBS Lett 417:28–32PubMedGoogle Scholar
  26. Villmann C, Bull L, Hollmann M (1997) Kainate binding proteins possess functional ion channel domains. J Neurosci 17:7634–7643PubMedGoogle Scholar
  27. Wirth KJ, Knobloch K (2001) Differential effects of dofetilide, amiodarone, and class Ic drugs on left and right atrial refractoriness and left atrial vulnerability in pigs. Naunyn-Schmiedebergs Arch Pharmacol 363:166–174PubMedGoogle Scholar

Voltage Clamp Studies on Calcium Channels

  1. Augustine GJ, Charlton MP, Smith RJ (1987) Calcium action in synaptic transmitter release. Annu Rev Neurosci 10:633–693PubMedGoogle Scholar
  2. Bean BP (1989) Classes of calcium channels in vertebrate cells. Annu Rev Physiol 51:376–384Google Scholar
  3. Berjukom S, Marksteiner R, Gapp F, Sinneger MJ, Hering S (2000) Molecular mechanism of calcium channel block by isradipine. Role of a drug-induced inactivated channel configuration. J Biol Chem 275:22114–22120Google Scholar
  4. Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Ann Rev Cell Dev Biol 16:521–555Google Scholar
  5. Cheng T-H, Lee F-Y, Wei J, Lin C-I (1996) Comparison of calcium-current in isolated atrial myocytes from failing and nonfailing human hearts. Mol Cell Biochem 157:157–162PubMedGoogle Scholar
  6. Foehring RC, Srcoggs RS (1994) Multiple high-threshold calcium currents in acutely isolated rat amygdaloid pyramidal cells. J Neurophysiol 71:433–436PubMedGoogle Scholar
  7. Gomez JP, Potreau D, Branka JE, Raymond G (1994) Developmental changes in Ca2+ currents from newborn rat cardiomyocytes in primary culture. Pflugers Arch 428:214–249Google Scholar
  8. Hering S, Aczél S, Klaus RL, Berjukow S, Striessnig J, Timin EN (1997) Molecular mechanism of use-dependent calcium channel block by phenylalkylamines: role of inactivation. Proc Natl Acad Sci U S A 94:13323–13328PubMedCentralPubMedGoogle Scholar
  9. Hockerman GH, Peterson BZ, Sharp E, Tanada TN, Scheuer T, Catterall WA (1997) Constriction of a high-affinity receptor site for dihydropyridine agonists and antagonists by single amino acid substitution in a non-L-type Ca2+ channel. Proc Natl Acad Sci USA 94:14906–14911PubMedCentralPubMedGoogle Scholar
  10. Johnson BD, Scheuer T, Catterall WA (1994) Voltage-dependent potentiation of L-type Ca2+ channels in skeletal muscles cells requires anchored cAMP-dependent protein kinase. Proc Natl Acad Sci 91:11492–11496PubMedCentralPubMedGoogle Scholar
  11. Koester HJ, Sakmann B (1998) Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagation action potentials and subthreshold excitatory potentials. Proc Natl Acad Sci U S A 95:9596–9601PubMedCentralPubMedGoogle Scholar
  12. Kraus RL, Hering S, Grabner M, Ostler D, Striessnig J (1998) Molecular mechanisms of diltiazem interaction with L-type Ca2+ channels. J Biol Chem 273:27205–27212PubMedGoogle Scholar
  13. Lacinová L, An HR, Xia J, Ito H, Klugbauer N, Triggle E, Hofmann F, Kass RS (1999) Distinction in the molecular determinants of charged and neutral dihydropyridine block of L-type calcium channels. J Pharmacol Exp Ther 289:1472–1479PubMedGoogle Scholar
  14. Lacinová L, Klugbauer N, Hofmann F (2000) State- and isoform-dependent interaction of isradipine with the α 1C L-type calcium channel. Pflügers Arch Eur J Physiol 440:50–60Google Scholar
  15. Margrie TW, Sakmann B, Urban NN (2001) Action potential propagation in mitral cell lateral dendrites is decremental and controls recurrent and lateral inhibition in the mammalian olfactory bulb. Proc Natl Acad Sci U S A 98:319–324PubMedCentralPubMedGoogle Scholar
  16. Markram H, Sakmann B (1994) Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc Natl Acad Sci U S A 91:5207–5211PubMedCentralPubMedGoogle Scholar
  17. McHugh D, Sharp EM, Scheuer T, Catterall WA (2000) Inhibition of L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain. Proc Natl Acad Sci U S A 97:12334–12338PubMedCentralPubMedGoogle Scholar
  18. Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235:46–52PubMedGoogle Scholar
  19. Morita H, Cousins H, Inoue H, Ito Y, Inoue R (1999) Predominant distribution of nifedipine-insensitive, high voltage-activated Ca2+ channels in the terminal mesenteric artery of guinea pig. Circ Res 85:596–605PubMedGoogle Scholar
  20. Narahash T, Tsunoo A, Yoshii M (1987) Characterization of two types of calcium channels in mouse neuroblastoma cells. J Physiol 38:231–249Google Scholar
  21. Peterson BZ, Johnson BD, Hockerman GH, Acheson M, Scheuer T, Catterall WA (1997) Analysis of the dihydropyridine receptor site of L-type calcium channels by alanine-scanning mutagenesis. J Biol Chem 272:18752–18758PubMedGoogle Scholar
  22. Scamps F, Mayoux E, Charlemagne D, Vassort G (1990) Calcium current in single cells isolated from normal and hypertrophied rat heart. Circ Res 67:199–208PubMedGoogle Scholar
  23. Sculptoreanu A, Rotman E, Takahasi M, Scheuer T, Catterall WA (1993) Voltage-dependent potentiation of the activity of cardiac L-type calcium channel α1 subunits due to phosphorylation by cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 90:10135–10139PubMedCentralPubMedGoogle Scholar
  24. Snutch TP, Sutton KG, Zamponi GW (2001) Voltage-dependent calcium channels – beyond dihydropyridine antagonists. Curr Opin Pharmacol 1:11–16PubMedGoogle Scholar
  25. Stephens GJ, Page KM, Burley JR, Berrow NS, Dolphin AC (1997) Functional expression of brain cloned α1E calcium channels in COS-7 cells. Pflugers Arch 433:525–532Google Scholar
  26. Stuart G, Spruston N (1995) Probing dendritic function with patch pipettes. Curr Opin Neurobiol 5:389–394PubMedGoogle Scholar
  27. Tohse N, Masuda H, Sperelakis N (1992) Novel isoform of Ca2+ channel in rat fetal cardiomyocytes. J Physiol (London) 451:295–306Google Scholar
  28. Waard MD, Campell KP (1995) Subunit regulation of the neuronal α 1A Ca2+ channel expressed in Xenopus oocytes. J Physiol (London) 485:619–634Google Scholar
  29. Wu S, Zhang M, Vest PA, Bhattacharjee A, Liu L, Li M (2000) A mifrabidile metabolite is a potent intracellular blocker of L-type Ca2+ currents in pancreatic β-cells. J Pharmacol Exp Ther 292:939–943PubMedGoogle Scholar
  30. Xu X, Rials SJ, Wu Y, Liu T, Marinchak RA, Kowey PR (2000) Effects of captopril treatment of renovascular hypertension on β-adrenergic modulation of L-type Ca2+ current. J Pharmacol Exp Ther 292:196–200PubMedGoogle Scholar
  31. Yang JC, Shan J, Ng KF, Pang P (2000) Morphine and methadone have different effects on calcium channel currents in neuroblastoma cells. Brain Res 870:199–203PubMedGoogle Scholar
  32. Young C, Huang Y-C, Lin C-H, Shen Y-Z, Gean P-W (2001) Selective enhancement of L-type calcium currents by corticotropin in acutely isolated rat amygdala neurons. Mol Pharmacol 59:604–611PubMedGoogle Scholar
  33. Zamponi GW (1997) Antagonist sites of voltage-dependent calcium channels. Drug Dev Res 42:131–143Google Scholar

Patch Clamp Studies on Chloride Channels

  1. Cliff WH, Frizzell RA (1990) Separate Cl- conductances activated by cAMP and Ca2+ in Cl(-)-secreting epithelial cells. Proc Natl Acad Sci U S A 87(13):4956–60PubMedCentralPubMedGoogle Scholar
  2. Frings S, Reuter D, Kleene SJ (2000) Neuronal Ca2+ activated Cl channels – homing in on an elusive channel species. Prog Neurobiol 60:247–289PubMedGoogle Scholar
  3. Jentsch TJ, Günther W (1997) Chloride channels: an emerging molecular picture. Bioessays 19:117–126PubMedGoogle Scholar
  4. Maertens C, Wie L, Droogmans G, Nilius B (2000) Inhibition of volume-regulated and calcium-activated chloride channels by the antimalarial mefloquine. J Pharmacol Exp Ther 295:29–36PubMedGoogle Scholar
  5. Pusch M, Liantonio A, Bertorello L, Accardi A, de Lucca A, Pierno S, Tortorella V, Camerino DC (2000) Pharmacological characterization of chloride channels belonging to the ClC family by the use of chiral clofibric acid derivatives. Mol Pharmacol 58:498–507PubMedGoogle Scholar

Inhibition of Hyperpolarization-Activated Channels

  1. Albaladejo P, Challande P, Kakou A, Benetos A, Labat C, Louis H, Safar ME, Lacolley P (2004) Selective reduction of heart rate by ivabradine: effect on the visco-elastic arterial properties in rats. J Hypertens 22:1739–1745PubMedGoogle Scholar
  2. Accili EA, DiFrancesco D (1996) Inhibition of the hyperpolarization-activated current (if) of rabbit SA node myocytes by niflumic acid. Pflugers Arch 431:757–762PubMedGoogle Scholar
  3. Accili EA, Robinson RB, DiFrancesco D (1997) Properties and modulation of I f in newborn versus adult SA node. Am J Physiol 272:H1549–H1552PubMedGoogle Scholar
  4. Accili EA, Proenza C, Baruscotti M, DiFrancesco D (2002) From funny current to HCN channels: 20 years of excitation. News Physiol Sci 17:32–37PubMedGoogle Scholar
  5. Baruscotti M, Bucchi A, DiFrancesco D (2005) Physiology and pharmacology of the cardiac pacemaker (“funny”) current. Pharmacol Ther 107:59–79PubMedGoogle Scholar
  6. Biel M, Schneider A, Wahl C (2002) Cardiac HCN channels: structure, function, and modulation. Trends Cardiovasc Med 12:206–2134PubMedGoogle Scholar
  7. Bois P, Bescond J, Renaudon B, Lenfant J (1996) Mode of action of bradycardic agent, S-16257, on ionic currents of rabbit sinoatrial node cells. Br J Pharmacol 118:1051–1057PubMedCentralPubMedGoogle Scholar
  8. Bucchi A, Baruscotti M, DiFrancesco D (2002) Current-dependent block of rabbit sino-atrial node If channels by Ivabradine. J Gen Physiol 120:1–13PubMedCentralPubMedGoogle Scholar
  9. Cerbai E, de Paoli P, Sartiani L, Lonardo G, Mugelli A (2003) Treatment with Irbesartan counteracts the functional remodeling of ventricular myocytes from hypertensive rats. J Cardiovasc Pharmacol 41:804–812PubMedGoogle Scholar
  10. Chatelier A, Renaudon B, Bescond J, El Chemaly A, Demion M, Bois P (2005) Calmodulin antagonist W7 directly inhibits f-type current in rabbit sino-atrial cells. Eur J Pharmacol 521:29–33PubMedGoogle Scholar
  11. Colin P, Ghaleh B, Monnet X, Hittinger L, Berdeaux A (2004) Effect of graded heart rate reduction with Ivabradine on myocardial oxygen consumption and diastolic time in exercising dogs. J Pharmacol Exp Ther 308:236–240PubMedGoogle Scholar
  12. Deplon E, Valenzuela C, Perez O, Franqueza L, Gay P, Snyders DJ, Tamargo J (1996) Mechanisms of block of human cloned potassium channel by the enantiomers of a new bradycardic agent: S-16257–2 and S-1620–2. Br J Pharmacol 117:1293–1301Google Scholar
  13. DiFrancesco D, Camm JA (2004) Heart rate lowering by specific and selective I f current inhibition with Ivabradine. Drugs 64:1757–1765PubMedGoogle Scholar
  14. DiFrancesco D, Mangoni M (1994) Modulation of single hyperpolarization-activated channels i f by cAMP in the rabbit sino-atrial node. J Physiol (London) 474:473–482Google Scholar
  15. DiFrancesco D, Noble D (1985) A model of cardiac electrical activity incorporating ionic pumps and concentration changes. Philos Trans R Soc Lond B Biol Sci 307(1133):353–98PubMedGoogle Scholar
  16. DiFrancesco P, Tortora D (1991) Direct activation of cardiac pacemaker channels by intracellular cyclic AMP. Nature 351:145–147PubMedGoogle Scholar
  17. DiFrancesco D, Ferroni A, Mazzanti M, Tromba C (1986) Properties of the hyperpolarizing-activated current (i f) in cells isolated from the rabbit sino-atrial node. J Physiol (London) 377:61–88Google Scholar
  18. Fabiato A, Fabiato F (1979) Calcium programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. J Physiol (London) 75:463–505Google Scholar
  19. Ishii TM, Takano M, Xie LH, Noma A, Ohmori H (1999) Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node. J Biol Chem 274:12835–12839PubMedGoogle Scholar
  20. Kaupp UB, Seifert R (2001) Molecular diversity of pacemaker channels. Annu Rev Physiol 63:235–257PubMedGoogle Scholar
  21. Leoni AL, Marionneau C, Demolombe S, Le Bouter S, Mangoni ME, Escande D, Charpentier F (2005) Chronic heart rate reduction remodels ion channel transcripts in the mouse sinoatrial node but not in the ventricle. Physiol Genomics 24:4–12PubMedGoogle Scholar
  22. Macri V, Proenza C, Agranovich E, Angoli D, Accili EA (2002) Separable gating mechanisms in a mammalian pacemaker channel. J Biol Chem 277:35939–35946PubMedGoogle Scholar
  23. Monnet X, Ghaleh B, Colin P, de Curzon OP, Guidicelli JF, Berdeaux A (2001) Effects of heart rate reduction with Ivabradine on exercise-induced myocardial ischemia and stunning. J Pharmacol Exp Ther 299:1133–1139PubMedGoogle Scholar
  24. Monnet X, Colin P, Ghaleh B, Hittinger L, Giudicelli JF, Berdeaux A (2004) Heart rate reduction during exercise-induced myocardial ischemia and stunning. Eur Heart J 25:579–586PubMedGoogle Scholar
  25. Moreno AP (2004) Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins. Cardiovasc Res 62:276–286PubMedGoogle Scholar
  26. Mulder P, Barbier S, Chagraoui A, Richard V, Henry JP, Lallemand F, Renet S, Lerebours G, Mahlberg-Gaudin F, Thuillez C (2004) Long-term heart rate reduction induced by the selective if current inhibitor Ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation 109:1674–1679PubMedGoogle Scholar
  27. Rigg L, Mattick PAD, Heath BM, Terrar DA (2003) Modulation of the hyperpolarization-activated current (I f) by calcium and calmodulin in the guinea-pig sino-atrial node. Cardiovasc Res 57:497–504PubMedGoogle Scholar
  28. Robinson RB, Siegelbaum SA (2003) Hyperpolarization-activated cation currents: from molecules to physiological function. Annu Rev Physiol 65:453–480PubMedGoogle Scholar
  29. Rocchetti M, Armato A, Cavalieri B, Micheletti M, Zaza A (1999) Lidocaine inhibition of the hyperpolarization-activated current in sinoatrial myocytes. J Cardiovasc Pharmacol 34:434–439PubMedGoogle Scholar
  30. Romanelli MN, Cerbai E, Dei S, Guandalini L, Martelli C, Martini E, Scapecchi S, Teodori E, Mugelli A (2005) Design, synthesis and preliminary biological evaluation of zatebradine analogues as potential blockers of hyperpolarization-activated current. Bioorg Med Chem 13:1211–1220PubMedGoogle Scholar
  31. Schipke JD, Büter I, Hohlfeld T, Schmitz-Spanke S, Gams E (2006) Selektive I f-Kanal-Hemmung: eine Alternative in der Behandlung der koronaren Herzkrankheit? Herz 31:55–74PubMedGoogle Scholar
  32. Simon L, Ghaleh B, Puybasset L, Giudicelli JF, Berdeaux A (1995) Coronary and hemodynamic effects of S 16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther 275:659–665PubMedGoogle Scholar
  33. Thollon C, Cambarrat C, Vian J, Prost JF, Peglion JL, Vilaine JP (1994) Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49. Br J Pharmacol 112:37–42PubMedCentralPubMedGoogle Scholar
  34. Thollon C, Bidouard JP, Cambarrat C, Lesage L, Reure H, Delescluse I, Vian J, Peglion JL, Vilaine JP (1997) Stereospecific in vitro and in vivo effects of the new sinus node inhibitor (+)-S 16257. Eur J Pharmacol 339:43–51PubMedGoogle Scholar
  35. Tsien RW, Rink J (1980) Neutral carrier ion-selective microelectrodes for measurements of intracellular free calcium. Biochim Biophys Acta 599:623–638PubMedGoogle Scholar
  36. Vilaine JP (2004) Selection et caracterisation pharmacologique de Procorolan, un inhibiteur selectif du courant pacemaker If. Therapie 59:495–505PubMedGoogle Scholar
  37. Vilaine JP, Bidouard JP, Lesage L, Reure H, Péglion JL (2003) Anti-ischemic effects of Ivabradine, a selective heart rate-reducing agent, in exercise-induced myocardial ischemia in pigs. J Cardiovasc Pharmacol 42:688–696PubMedGoogle Scholar

Measurement of Cytosolic Calcium with Fluorescent Indicators

  1. Busse R, Lamontagne D (1991) Endothelium-derived bradykinin is responsible for the increase in calcium produced by angiotensin-converting enzyme inhibitors in human endothelial cells. Naunyn Schmiedebergs Arch Pharmacol 344:26–129Google Scholar
  2. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca+2 indicators with improved fluorescence properties. J Biol Chem 260:3440–3450PubMedGoogle Scholar
  3. Hayashi H, Miyata H (1994) Fluorescence imaging of intracellular Ca2+. J Pharmacol Toxicol Methods 31:1–10PubMedGoogle Scholar
  4. Hock FJ, Wirth K, Albus U, Linz W, Gerhards HJ, Wiemer G, Henke S, Breipohl G, König W, Knolle J, Schölkens BA (1991) Hoe 140 a new potent and long acting bradykinin antagonist: in vitro studies. Br J Pharmacol 102:769–773PubMedCentralPubMedGoogle Scholar
  5. Lee HC, Smith N, Mohabir R, Clusin WT (1987) Cytosolic calcium transients from the beating mammalian heart. Proc Natl Acad Sci U S A 84:7793–7797PubMedCentralPubMedGoogle Scholar
  6. Lückhoff A, Pohl U, Mülsch A, Busse R (1988) Differential role of extra- and intracellular calcium in the release of EDRF and prostacyclin from cultured endothelial cells. Br J Pharmacol 95:189–196PubMedCentralPubMedGoogle Scholar
  7. Makujina SR, Abebe W, Ali S, Mustafa SJ (1995) Simultaneous measurement of intracellular calcium and tension in vascular smooth muscle: validation of the everted ring preparation. J Pharmacol Toxicol Methods 34:157–163PubMedGoogle Scholar
  8. Monteith GR, Chen S, Roufogalis BD (1994) Measurement of Ca2+ pump-mediated efflux in hypertension. J Pharmacol Toxicol Methods 31:117–124PubMedGoogle Scholar
  9. Tsien RY, Pozzan T, Rink TJ (1982) Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new intracellularly trapped fluorescent indicator. J Cell Biol 94:325–334PubMedGoogle Scholar
  10. Wiemer G, Popp R, Schölkens BA, Gögelein H (1994) Enhancement of cytosolic calcium, prostaglandin and nitric oxide by bradykinin and the ACE inhibitor ramiprilat in porcine brain capillary endothelial cells. Brain Res 638:261–266PubMedGoogle Scholar
  11. Yanagisawa T, Kawada M, Taira N (1989) Nitroglycerine relaxes canine coronary arterial smooth muscle without reducing intracellular Ca2+ concentrations measured with fura-2. Br J Pharmacol 98:469–482PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Michael Gralinski
    • 1
  • Liomar A. A. Neves
    • 1
  • Olga Tiniakova
    • 1
  1. 1.CorDynamics, Inc.ChicagoUSA

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