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Ion Channels in Cardiac Fibroblasts: Link to Mechanically Gated Channels and their Regulation

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Mechanically Gated Channels and their Regulation

Part of the book series: Mechanosensitivity in Cells and Tissues ((MECT,volume 6))

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Abstract

Cardiac fibroblasts according to a number of authors have delayed rectifier current (IK), transient potassium current (Ito), inward rectifier potassium current (IKir), Ca2+-activated K+ current (IK(Ca)), TTX-sensitive sodium voltage-gated current (INa.TTX), TTX-sensitive sodium voltage-gated current (INa.TTXR), volume-sensitive chloride current (ICl.vol), voltage gated proton current (IHv), non-selective cation currents, besides mechanosensitive MG currents reported by Kamnkin et al. Manuscript describes single mechanically gated channels (MGCs), recorded simultaneously with whole cell MG currents. It demonstrates that cellular compression activates current, flowing through single MGCs (recorded in cell attached mode), along with whole cell MGC current (recorded in whole cell mode), which leads to generation of mechanically induced potentials (MIP). Cellular stretching inactivates those currents. Gd3+, cytochalasin D and colchicine inhibit both the whole-cell MG currents and single MG currents activity. All of those currents, which are mentioned above, together with MG currents contribute to alterations of fibroblast membrane potential (resting potentials and MIPs). Since fibroblasts are connected with cardiomyocytes via gap junctions, hyperpolarization of resting potential, triggered by cellular stretching, depolarization of the resting potentials, triggered by cellular compression, and the repolarization of the MIPs may potentially prolong the action potential duration in cardiomyocytes thereby predisposing the heart to arrhythmia.

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References

  • Adler CP, Ringlage WP, Bohm N (1981) DNS-Gehalt und Zellzahl in Herz und Leber von Kindern. Pathol Res Pract 172:25–41

    Article  PubMed  CAS  Google Scholar 

  • Baumgarten CM, Clemo HF (2003) Swelling-activated chloride channels in cardiac physiology and pathophysiology. Prog Biophys Mol Biol 82:25–42

    Article  PubMed  CAS  Google Scholar 

  • Benamer N, Maati HMO, Demolombe S, Cantereau A, Delwail A, Bois P, Bescond J, Faivre J (2009) Molecular and functional characterization of a new potassium conductance in mouse ventricular fibroblasts. J Mol Cell Cardiol 46:508–517

    Article  PubMed  CAS  Google Scholar 

  • Benamer N, Fares N, Bois P, Faivre J (2011) Electrophysiological and functional effects of sphingosine-1-phosphate in mouse ventricular fibroblasts. Biochem Biophys Res Commun 408:6–11

    Article  PubMed  CAS  Google Scholar 

  • Boyett MR, Honjo H, Kodama I (2000) The sinoatrial node, a heterogenous pacemaker structure. Cardiovasc Res 47:658–687

    Article  PubMed  CAS  Google Scholar 

  • Camelliti P, Borg TK, Kohl P (2005) Structural and functional characterization of cardiac fibroblasts. Cardiovasc Res 65:40–51

    Article  PubMed  CAS  Google Scholar 

  • Carver W, Fuseler JW (2010) Mechanical stretch-induced reorganization of the cytoskeleton and the small GTPase Rac in cardiac fibroblasts. In: Mechanosensitivity in Cells and Tissues 3. Mechanosensitivity of the Heart. Andre Kamkin and Irina Kiseleva (eds.). Springer, Berlin, pp 35–54

    Google Scholar 

  • Chilton L, Ohya S, Freed D, George E, Drobic V, Shibukawa Y, MacCannell KA, Imaizumi Y, Clark RB, Dixon IMC, Giles WR (2005) K+ currents regulate the resting membrane potential, proliferation, and contractile responses in ventricular fibroblasts and myofibroblasts. Am J Physiol Heart Circ Physiol 288:H2931-H2939

    Article  PubMed  CAS  Google Scholar 

  • Clapham DE, Runnels LW, Strubing C (2001) The TRP ion channel family. Nat Rev Neurosci 2:387–396

    Article  PubMed  CAS  Google Scholar 

  • Coetzee WA, Amarillo Y, Chiu J, Chow A, Lau D, McCormack T, Moreno H, Nadal MS, Ozaita A, Pountney D, Saganich M, Vega-Saenz de Miera E, Rudy B (1999) Molecular diversity of K1 channels. Ann N Y Acad Sci 868:233–285

    Article  PubMed  CAS  Google Scholar 

  • Decoursey TE (2003) Voltage-gated proton channels and other proton transfer pathways. Physiol Rev 83:475–579

    PubMed  CAS  Google Scholar 

  • Du X, Gao Z, Lau C, Chiu S, Tse H, Baumgarten CM, Li G (2004) Differential effects of tyrosine kinase inhibitors on volume-sensitive chloride current in human atrial myocytes: evidence for dual regulation by Src and EGFR kinases. J Gen Physiol 123:427–439

    Article  PubMed  CAS  Google Scholar 

  • El Chemaly A, Guinamard R, Demion M, Fares N, Jebara V, Faivre JF, Bois P (2006) A voltage-activated proton current in human cardiac fibroblasts. Biochem Biophys Res Commun 340(2):512–516

    Article  PubMed  CAS  Google Scholar 

  • Goshima K (1970) Formation of nexuses and electrotonic transmission between myocardial and FL cells in monolayer culture. Exp Cell Res 63(1):124–130

    Article  PubMed  CAS  Google Scholar 

  • Goshima K, Tonomura Y (1969) Synchronized beating of embryonic mouse myocardial cells mediated by FL cells in monolayer culture. Exp Cell Res 56(2):387–392

    Article  PubMed  CAS  Google Scholar 

  • Hamill OP, Martinac B (2001) Molecular basis of mechanotransduction in living cells. Physiol Rev 81(2):685–740

    PubMed  CAS  Google Scholar 

  • Hatano N, Itoh Y, Muraki K (2009) Cardiac fibroblasts have functional TRPV4 activated by 4α-phorbol 12,13-didecanoate. Life Sci 85:808–814

    Article  PubMed  CAS  Google Scholar 

  • He M, Liu W, Sun H, Wu W, Liu J, Tse H, Lau C, Li G (2011) Effects of ion channels on proliferation in cultured human cardiac fibroblasts. J Mol Cell Cardiol 51:198–206

    Article  PubMed  CAS  Google Scholar 

  • Hiraoka M, Kawano S, Hirano Y, Furukawa T (1998) Role of cardiac chloride currents in changes in action potential characteristics and arrhythmias. Cardiovasc Res 40:23–33

    Article  PubMed  CAS  Google Scholar 

  • Isenberg G, Kazanski V, Kondratev D, Gallitelli MF, Kiseleva I, Kamkin A (2003) Differential effects of stretch and compression on membrane currents and [Na+]c in ventricular myocytes. Prog Biophys Mol Biol 82(1–3):43–56

    Article  PubMed  CAS  Google Scholar 

  • Kaab S, Dixon J, Duc J, Ashen D, Näbauer M, Beuckelmann DJ, Steinbeck G, McKinnon D, Tomaselli GF (1998) Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation 98:1383–1393

    Article  PubMed  CAS  Google Scholar 

  • Kamkin A, Kiseleva I, Kircheis R, Kositzky G (1988) Abhandlungen der Akademie der Wissenschaften der DDR (Abteilung Mathematik – Naturwissenschaft – Technik) 1:103

    Google Scholar 

  • Kamkin A, Kiseleva I, Wagner KD, Lammerich A, Bohm J, Persson PB, Günther J (1999) Mechanically induced potentials in fibroblasts from human right atrium. Exp Physiol 84:347–356

    Article  PubMed  CAS  Google Scholar 

  • Kamkin A, Kiseleva I, Isenberg G (2000) Stretch-activated currents in ventricular myocytes: amplitude and arrhythmogenic effects increase with hypertrophy. Cardiovasc Res 48(3):409–420

    Article  PubMed  CAS  Google Scholar 

  • Kamkin A, Kiseleva I, Wagner KD, Scholz H, Theres H, Kazanski V, Lozinsky I, Gunther J, Isenberg G (2001) Mechanically induced potentials in rat atrial fibroblasts depend on actin and tubulin polymerisation. Pflugers Arch 442:487–497

    Article  PubMed  CAS  Google Scholar 

  • Kamkin A, Kiseleva I, Wagner KD, Pylaev A, Leiterer KP, Theres H, Scholz H, Günther J, Isenberg G (2002) A possible role for atrial fibroblasts in postinfarction bradycardia. Am J Physiol 282:H842-H849

    CAS  Google Scholar 

  • Kamkin A, Kiseleva I, Isenberg G (2003a) Activation and inactivation of a non-selective cation conductance by local mechanical deformation of acutely isolated cardiac fibroblasts. Cardiovasc Res 57:793–803

    Article  CAS  Google Scholar 

  • Kamkin A, Kiseleva I, Isenberg G, Wagner KD, Günther J, Theres H, Scholz H (2003b) Cardiac fibroblasts and the mechano-electric feedback mechanism in healthy and diseased hearts. Prog Biophys Mol Biol 82:111–120

    Article  CAS  Google Scholar 

  • Kamkin A, Kirischuk S, Kiseleva I (2010a) Single mechano-gated channels activated by mechanical deformation of acutely isolated cardiac fibroblasts from rats. Acta Physiol 199:277–292

    CAS  Google Scholar 

  • Kamkin A, Kiseleva I, Lozinsky I (2010b) The role of mechanosensitive fibroblasts in the heart: evidence from acutely isolated single cells, cultured cells and from intracellular microelectrode recordings on multicellular preparations from healthy and diseased cardiac tissue. In: Mechanosensitivity in Cells and Tissues 3. Mechanosensitivity of the Heart. Andre Kamkin and Irina Kiseleva (eds.) Springer, Berlin, pp 239–266

    Google Scholar 

  • Kamkin A, Kiseleva I, Wagner KD, Lozinsky I, Günther J, Scholz H (2003c) Mechanically induced potentials in atrial fibroblasts from rat hearts are sensitive to hypoxia/reoxygenation. Pflügers Arch 446:169–174

    CAS  Google Scholar 

  • Kamkin A, Scholz H, Kiseleva I (2011)  Cardiac fibroblasts in normal and diseased heart: single mechanically-gated ion channels, mechanosensitive currents and mechanically induced potentials in isolated cells and tissue. In: Turner NA (ed) The cardiac fibroblast. Research Signpost, Kerala, pp 1–16

    Google Scholar 

  • Kiseleva IS, Kamkin AG, Kircheis R, Kositski GI (1987) Intercellular electrotonic interactions in the cardiac sinus node in the frog. Dokl Akad Nauk SSSR, 292(6):1502–1505

    PubMed  CAS  Google Scholar 

  • Kiseleva I, Kamkin A, Kohl P, Lab M (1996) Calcium and mechanically induced potentials in fibroblasts of rat atrium. Cardiovasc Res 32:98–111

    PubMed  CAS  Google Scholar 

  • Kiseleva I, Kamkin A, Pylaev A, Kondratjev D, Leiterer KP, Theres H, Wagner KD, Persson PB, Günther J (1998) Electrophysiological properties of mechanosensitive atrial fibroblasts from chronic infarcted rat heart. J Mol Cell Cardiol 30:1083–1093

    Article  PubMed  CAS  Google Scholar 

  • Kohl P, Camelliti P, Burton FL, Smith GL (2005) Electrical coupling of fibroblasts and myocytes: relevance for cardiac propagation. J Electrocardiol 38:45–50

    Article  PubMed  Google Scholar 

  • Lammerding J, Kamm PD, Lee RT (2004) Mechanotransduction in cardiac myocytes. Ann N Y Acad Sci 1015:53–70

    Article  PubMed  Google Scholar 

  • Li G, Sun H, Chen J, Zhou Y, Tse H, Lau C (2009) Characterization of Multiple Ion Channels in Cultured Human Cardiac Fibroblasts. PLoS ONE 4(10):e7307. doi:10.1371/journal.pone.0007307

    Article  PubMed  Google Scholar 

  • Lopatin AN, Nichols CG (2001) Inward rectifiers in the heart: an update on IK1. J Mol Cell Cardiol 33:625–638

    Article  PubMed  CAS  Google Scholar 

  • Meissner M, Weissgerber P, Londono JEC, Prenen J, Link S, Ruppenthal S, Molkentin JD, Lipp P, Nilius B, Freichel M, Flockerzi V (2011) Moderate calcium channel dysfunction in adult mice with inducible cardiomyocyte-specific excision of the cacnb2 gene. J Biol Chem 286(18):15875–15882

    Article  PubMed  CAS  Google Scholar 

  • Montell C (2005) The TRP superfamily of cation channels. Sci STKE 2005:1–24

    Article  Google Scholar 

  • Nilius B, Talavera K, Owsianik G, Prenen J, Droogmans G, Voets T (2005) Gating of TRP channels: a voltage connection? J Physiol 567:35–44

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Yada T, Ohno-Shosaku T, Oiki S, Ueda S, Machida K (1984) Exogenous ATP induces electrical membrane responses in fibroblasts. Exp Cell Res 152:552–557

    Article  PubMed  CAS  Google Scholar 

  • Oren RV, Clancy CE (2010) Determinants of heterogeneity, excitation and conduction in the sinoatrial node: a model study. PLOS Comp Biol 6(12):e1001041. doi:10.1371/journal.pcbi.1001041

    Article  CAS  Google Scholar 

  • Oudit GY, Kassiri Z, Sah R, Ramirez RJ, Zobel C, Backx PH (2001) The molecular physiology of the cardiac transient outward potassium current Ito in normal and diseased myocardium. J Mol Cell Cardiol 33:851–872

    Article  PubMed  CAS  Google Scholar 

  • Owsianik G, Talavera K, Voets T, Nilius B (2006) Permeation and selectivity of TRP channels. Annu Rev Physiol 68:685–717

    Article  PubMed  CAS  Google Scholar 

  • Roden DM, Balser JR, George AL Jr (2002) Cardiac ion channels. Annu Rev Physiol 64:431–475

    Article  PubMed  CAS  Google Scholar 

  • Rodrigues AR, Arantes EC, Monje F, Stuhmer W, Varanda WA (2003) Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel Kv1.3. Br J Pharmacol 139:1180–1186

    Article  PubMed  CAS  Google Scholar 

  • Rook MB, van Ginneken ACG, De Jonge B, El Aoumari A, Gros D, Jongsma HJ (1992) Differences in gap junction channels between cardiac myocytes, fibroblasts, and heterologous pairs. Cell Physiol 32:C959-C977

    Google Scholar 

  • Rose RA, Giles WR (2008) Natriuretic peptide C receptor signaling in the heart and vasculature. J Physiol 586(2):353–366

    Article  PubMed  CAS  Google Scholar 

  • Rose RA, Hatano N, Ohya S, Imaizumi Y, Giles WR (2007) C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signaling. J Physiol 580(1):255–274

    Article  PubMed  CAS  Google Scholar 

  • Sachs F, Morris CE (1998) Mechanosensitive ion channels in nonspecialized cells. Rev Physiol Biochem Pharmacol 132:1–77

    Article  PubMed  CAS  Google Scholar 

  • Saito T, Fujiwara Y, Fujiwara R, Hasegawa H, Kibira S, Miura H, Miura M (2002) Role of augmented expression of intermediate conductance Ca2+-activated K+ channels in postischaemic heart. Clin Exp Pharmacol Physiol 29:324–329

    Article  PubMed  CAS  Google Scholar 

  • Schram G, Pourrier M, Nattel S (2002) Differential distribution of cardiac ion channel expression as a basis for regional specialization in electrical function. Circ Res 90:939–950

    Article  PubMed  CAS  Google Scholar 

  • Shibukawa Y, Chilton EL, MacCannell KA, Clark RB, Giles WR (2005) K+ currents activated by depolarization in cardiac fibroblasts. Biophys J 88:3924–3935

    Article  PubMed  CAS  Google Scholar 

  • Shieh C-C, Coghlan M, Sullivan JP, Gopalakrishnan M (2000) Potassium channels: molecular defects, diseases, and therapeutic opportunities. Pharmacol Rev 52:557–594

    PubMed  CAS  Google Scholar 

  • Spach MS, Boineau JP (1997) Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias. Pacing Clin Electrophysiol 20:397–413

    Article  PubMed  CAS  Google Scholar 

  • Tamargo J, Caballero R, Gomez R, Valenzuela C, Delpon E (2004) Pharmacology of cardiac potassium channels. Cardiovasc Res 62:9–33

    Article  PubMed  CAS  Google Scholar 

  • Thampatty B, Wang J (2008) Mechanobiology of fibroblasts. In: Mechanosensitivity in Cells and Tissues 1. Mechanosensitive ion channels. Andre Kamkin and Irina Kiseleva (eds.) Springer, Berlin, pp 351–378

    Google Scholar 

  • Tombola F, Ulbrich MH, Isacoff EY (2008) The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor. Neuron 58:546–556

    Article  PubMed  CAS  Google Scholar 

  • Tsuchiya W, Okada Y, Yano J, Inouye A, Sasaki S, Doida Y (1981) Effects of cytochalasin B and local anesthetics on electrical and morphological properties in L cells. Exp Cell Res 133:83–92

    Article  PubMed  CAS  Google Scholar 

  • Vergara C, Latorre R, Marrion NV, Adelman JP (1998) Calcium-activated potassium channels. Curr Opin Neurobiol 8(3):321–329

    Article  PubMed  CAS  Google Scholar 

  • Vliegen HW, Van Der Laarse A, Cornelisse CJ, Eulderink F (1991) Myocardial changes in pressure overload-induced left ventricular hypertrophy. A study on tissue composition, polyploidization and multinucleation. Eur Heart J 12:488–494

    PubMed  CAS  Google Scholar 

  • Walsh KB, Zhang J (2008) Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C. Am J Physiol Heart Circ Physiol 294:H1010–H1017

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Sung RJ, Lin M, Wu S (2006) Contribution of BKCa-channel activity in human cardiac fibroblasts to electrical coupling of cardiomyocytes-fibroblasts. J Membr Biol 213:175–185

    Article  PubMed  Google Scholar 

  • Wible BA, De Biasi M, Majumder K, Taglialatela M, Brown AM (1995) Cloning and functional expression of an inwardly rectifying K+ channel from human atrium. Circ Res 76:343–350

    Article  PubMed  CAS  Google Scholar 

  • Wolk R, Cobbe SM, Hicks MN, Kane KA (1999) Functional, structural, and dynamic basis of electrical heterogeneity in healthy and diseased cardiac muscle: implications for arrhythmogenesis and anti-arrhythmic drug therapy. Pharmacol Ther 84:207–231

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Tuteja D, Zhang Z, Xu D, Zhang Y, Rodriguez J, Nie L, Tuxson HR, Young JN, Glatter KA, Vasquez J, Yamoah EN, Chiamvimonvat N (2003) Molecular identification and functional roles of a Ca2+-activated K+ channel in human and mouse hearts. J Biol Chem 278(49):49085–49094

    Article  PubMed  CAS  Google Scholar 

  • Yellen G (2002) The voltage-gated potassium channels and their relatives. Nature 419:35–42

    Article  PubMed  CAS  Google Scholar 

  • Yue L, Xie J, Nattel S (2011) Molecular determinants of cardiac fibroblast electrical function and therapeutic implications for atrial fibrillation. Cardiovasc Res 89:744–753

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Gao F, Popov VL, Wen JW, Hamill OP (2000) Mechanically gated channel activity in cytoskeleton-deficient plasma membrane blebs and vesicles from Xenopus oocytes. J Physiol 523:117–130

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the Russian Foundation for Basic Research (grant no. 09–04-01277-a). Department of Fundamental and Applied Physiology (Professor and Chairman – Andre Kamkin) was supported by Ministry of Education and Science of the Russian Federation. The Order of Ministry of Education and Science of the Russian Federation No. 743 from 01 July 2010, Supplement, Event 4.4, the Period of Financing 2010–2019.

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Abramochkin, D.V., Lozinsky, I., Kamkin, A. (2012). Ion Channels in Cardiac Fibroblasts: Link to Mechanically Gated Channels and their Regulation. In: Kamkin, A., Lozinsky, I. (eds) Mechanically Gated Channels and their Regulation. Mechanosensitivity in Cells and Tissues, vol 6. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5073-9_7

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