Canadian Journal of Anesthesia

, Volume 49, Issue 2, pp 151–164 | Cite as

Calcium channels — basic aspects of their structure, function and gene encoding; anesthetic action on the channels — a review

  • Michiaki Yamakage
  • Akiyoshi Namiki
General Anesthesia



To review recent findings concerning Ca2+ channel subtype/structureAunction from electrophysiological and molecular biological studies and to explain Ca2+ channel diseases and the actions of anesthetics on Ca2+ channels.


The information was obtained from articles published recently and from our published work.

Principal findings

L’oltage-dependent Ca2+ channels serve as one of the important mechanisms for Ca2+ influx into the cells, enabling the regulation of intracellular concentration of free Ca2+. Recent advances both in electrophysiology and in molecular biology have made it possible to observe channel activity directly and to investigate channel functions at molecular levels. The Ca2+ channel can be divided into subtypes according to electrophysiological characteristics, and each subtype has its own gene. The L-type Ca2+ channel is the target of a large number of clinically important drugs, especially dihydropyridines, and binding sites of Ca2+ antagonists have been clarified. The effects of various kinds of anesthetics in a variety of cell types have been demonstrated, and some clinical effects of anesthetics can be explained by the effects on Ca2+ channels. It has recently become apparent that some hereditary diseases such as hypokalemic periodic paralysis result from calcium channelopathies.


Recent advances both in electrophysiology and in molecular biology have made it possible to clarify the Ca2+ channel structures, functions, genes, and the anesthetic actions on the channels in detail. The effects of anesthetics on the Ca2+ channels either of patients with hereditary channelopathies or using gene mutation techniques are left to be discovered.


Volatile Anesthetic Malignant Hyperthermia Familial Hemiplegic Migraine Gallopamil Malignant Hyperthermia Susceptibility 
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.

Revue : notions de base sur la structure, la fonction et l’encodage génétique des canaux calciques et action des anesthésiques sur ces canaux



Passer en revue les découvertes récentes concernant le sous-type, la structure et la fonction du canal Ca2+ à partir des études électrophysiologiques et biologiques moléculaires et expliquer les lésions des canaux Ca2+ et les actions des anesthésiques sur ces canaux.


L’information provient d’articles publiés récemment et de nos travaux publiés.

Constatations principales

Les canaux Ca2+ voltage-dépendants sont l’un des importants mécanismes pour le flux entrant de Ca2+ dans les cellules, ce qui facilite la régulation de la concentration intracellulaire de Ca2+ libre. Les progrès récents en électrophysiologie et en biologie moléculaire ont permis d’observer directement l’activité des canaux et d’étudier leurs fonctions au niveau moléculaire. Les canaux Ca2+ peuvent être divisés en sous-types selon les caractéristiques électrophysiologiques et chaque sous-type a son propre gène. Le type L de canal Ca2+ est la cible d’un grand nombre de médicaments importants en clinique, spécialement les dihydropyridines, et les antagonistes des sites de liaison du Ca2+ ont été mis en évidence. Les effets de différentes classes d’anesthésiques dans une diversité de types de cellules ont été démontrés et certains effets cliniques des anesthésiques peuvent être expliqués par les effets sur les canaux Ca2+. Récemment, il est devenu clair que certaines affections héréditaires, comme la paralysie périodique hypokaliémique, résulte de pathologies des canaux calciques.


Les découvertes récentes en électrophysiologie et en biologie moléculaire ont permis de clarifier les structures, fonctions et gènes des canaux Ca2+ et de fournir des détails sur les actions des anesthésiques sur les canaux. Il reste à découvrir les effets des anesthésiques sur les canaux Ca2+ des patients atteints de pathologies héréditaires des canaux calciques ou à utiliser des techniques de mutation génétique.


  1. 1.
    Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature 1994; 372: 231–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Ghosh A, Greenberg ME. Calcium signaling in neurons: molecular mechanisms and cellular consequences. Science 1995; 268: 239–47.PubMedCrossRefGoogle Scholar
  3. 3.
    Borle AB. Control, modulation, and regulation of cell calcium. Rev Physiol Biochem Pharmacol 1981; 90: 13–153.PubMedCrossRefGoogle Scholar
  4. 4.
    Poelaert J, Roosens C Perioperative use of dihydropyridine calcium channel blockers. Acta Anaesthesiol Scand 2000; 44: 528–35.PubMedCrossRefGoogle Scholar
  5. 5.
    Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 1981; 391: 85–100.PubMedCrossRefGoogle Scholar
  6. 6.
    Varadi G, Strobeck M, Koch S, Caglioti L, Zucchi C, Palyi G Molecular elements of ion permeation and selectivity within calcium channels. Crit Rev Biochem Mol Biol 1999; 34: 181–214.PubMedCrossRefGoogle Scholar
  7. 7.
    Hagiwara S, Ozawa S, Sand Q l’oltage clamp analysis of two inward current mechanisms in the egg cell membrane of a starfish. J Gen Physiol 1975; 65: 617–44.PubMedCrossRefGoogle Scholar
  8. 8.
    Reuter FL Diversity and function of presynaptic calcium channels in the brain. Curr Opin Neurobiol 1996; 6: 331–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Nowycky MC, Fox AP, Tsien RW. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature 1985; 316: 440–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Fox AP, Nowycky MC, Fsien RW. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol 1987; 394: 149–72.PubMedGoogle Scholar
  11. 11.
    Fox AP, Nowycky MC, Fsien R W. Single -channel recordings of three types of calcium channels in chick sensory neurones. J Physiol 1987; 394: 173–200.PubMedGoogle Scholar
  12. 12.
    Ferroni A, Mancinelli E, Camgni S, Wanke E. Two high voltage-activated calcium currents are present in isolation in adult rat spinal neurons. Biochem Bioph Res Commun 1989; 159: 379–84.CrossRefGoogle Scholar
  13. 13.
    Plummer MR, Hess P. Reversible uncoupling of inactivation in N-type calcium channels. Nature 1991; 351: 657–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Fisher FE, Bourque CW. Distinct -agatoxin-sensitive calcium currents in somata and axon terminals of rat supraoptic neurons. J Physiol 1995; 489(Pt. 2): 383–8.PubMedGoogle Scholar
  15. 15.
    Llinas R, Sugimori M, Lin J-W, Cherksey B. Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison. Proc Natl Acad Sci USA 1989; 86: 1689–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Randall A, Fsien RW. Pharmacological dissection of multiple types of Ca2 + channel currents in rat cerebellar granule neurons. J Neurosci 1995; 15: 2995–3012.PubMedGoogle Scholar
  17. 17.
    Llinás R, Tarom T Properties and distribution of ionic conductances generating electroresponsiveness of mammalian inferior olivary neurones in vitro. J Physiol 1981; 315: 569–84.PubMedGoogle Scholar
  18. 18.
    Pearson HA, Sutton KG, Scott RH, Dolphin AC Characterization of Ca2 + channel currents in cultured rat cerebellar granule neurones. J Physiol 1995; 482: 493–509.PubMedGoogle Scholar
  19. 19.
    Catterall WA Structure and function of voltage-sensitive ion channels. Science 1988; 242: 50–61.PubMedCrossRefGoogle Scholar
  20. 20.
    Posset M, Jaimovich P, Delpont P, Pazdunski M [3H]Nitrendipine receptors in skeletal muscle. Properties and preferential localization in transverse tubules. J Biol Chem 1983; 258: 6086–92.Google Scholar
  21. 21.
    Varadi G, Mori T, Mikala G, Schwartz A Molecular determinants of Ca2 + channel function and drug action. Trends Pharmacol Sci 1995; 16: 43–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Pakahashi M, Seager MJ, Jones JP, Reber BFX, Catterall WA Subunit structure of dihydropyridine-sensitive calcium channels from skeletal muscle. Proc Natl Acad Sci USA 1987; 84: 5478–82.CrossRefGoogle Scholar
  23. 23.
    Panabe P, Pakeshima H, Mikami A, et al. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature 1987; 328: 313–8.CrossRefGoogle Scholar
  24. 24.
    Pllis SB, Williams MP, Ways NR, et al. Sequence and expression of mRNAs encoding the1 and2 subunits of a DHP-sensitive calcium channel. Science 1988; 241: 1661–4.CrossRefGoogle Scholar
  25. 25.
    Ruth P, Röhrkasten A, Biel M, et al. Primary structure of the β subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 1989; 245: 1115–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Jay SD, Pllis SB, McCue AP, et al. Primary structure of the D subunit of the DHP-sensitive calcium channel from skeletal muscle. Science 1990; 248: 490–2.PubMedCrossRefGoogle Scholar
  27. 27.
    Jan LY, Jan TN. l’oltage-sensitive ion channels. Cell 1989; 56: 13–25.PubMedCrossRefGoogle Scholar
  28. 28.
    Stühmer W, Conti P, Suzuki H, et al. Structure parts involved in activation and inactivation of the sodium channel. Nature 1989; 339: 597–603.PubMedCrossRefGoogle Scholar
  29. 29.
    McCleskey PW, Womack MD, Fieber LA Structural properties of voltage-dependent calcium channels. Int Rev Cytol 1993; 137C: 39–54.PubMedGoogle Scholar
  30. 30.
    Kostyuk PG Diversity of calcium ion channels in cellular membranes. Neuroscience 1989; 28: 253–61.PubMedCrossRefGoogle Scholar
  31. 31.
    Bond A, Grillner P, Mercuri NB, Bernardi G L-type calcium channels mediate a slow excitatory synaptic transmission in rat midbrain dopaminergic neurons. J Neurosci 1998; 18: 6693–703.Google Scholar
  32. 32.
    Protti DA, Piano I. Calcium currents and calcium signaling in rod bipolar cells of rat retinal slices. J Neurosci 1998; 18: 3715–24.PubMedGoogle Scholar
  33. 33.
    Witcher DR, De Waard M, Sakamoto J, et al. Subunit identification and reconstitution of the N-type Ca2+ channel complex purified from brain. Science 1993; 261: 486–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Miller RJ. Multiple calcium channels and neuronal function. Science 1987; 235: 46–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Stanley PP, Atrakchi AH Calcium currents recorded from a vertebrate presynaptic nerve terminal are resistant to the dihydropyridine nifedipine. Proc Natl Acad Sci USA 1990; 87: 9683–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Piu H, De Waard M, Scott VES, Gurnett CA, Lennon VA, Campbell KP. Identification of three subunits of the high-affinity □ -conotoxin MVTIC-sensitive Ca2 + channel. J Biol Chem 1996; 271: 13804–10.CrossRefGoogle Scholar
  37. 37.
    Plinás RR The intrinsic electrophysiological properties of mammalian neurons: insight into central nervous system function. Science 1988; 242: 1654–64.CrossRefGoogle Scholar
  38. 38.
    Avery RB, Johnston D Multiple channel types contribute to the low-voltage-activated calcium current in hippocampal CA3 pyramidal neurons. J Neurosci 1996; 16: 5567–82.PubMedGoogle Scholar
  39. 39.
    Prtel SI, Prtel PA Low-voltage-activated T-type Ca2 + channels. TIPS 1997; 18: 37–42.Google Scholar
  40. 40.
    Moreno DH Molecular and functional diversity of voltage-gated calcium channels. Ann New York Acad Sci 1999; 868: 102–17.CrossRefGoogle Scholar
  41. 41.
    Prtel PA, Campbell KP, Harpold MM, et al. Nomenclature of voltage-gated calcium channels (Letter). Neuron 2000; 25: 533–5.CrossRefGoogle Scholar
  42. 42.
    Powers PA, Scherer SW, Psui P-C, Gregg RG, Hogan K Localization of the gene encoding the α2/□ sub-unit (CACNL2A) of the human skeletal muscle voltage-dependent Ca2+ channel to chromosome 7q21-q22 by somatic cell hybrid analysis. Genomics 1994; 19: 192–3.PubMedCrossRefGoogle Scholar
  43. 43.
    Williams MP, Brust PP, Peldman DH, et al. Structure and functional expression of an-conotoxin-sensitive human N-type calcium channel. Science 1992; 257: 389–95.PubMedCrossRefGoogle Scholar
  44. 44.
    Birnbaumer P, Qin N, Olcese R, et al. Structure and functions of calcium channel β subunits. J Bioenerg Biomembr 1998; 30: 357–75.PubMedCrossRefGoogle Scholar
  45. 45.
    Powers PA, Piu S, Hogan K, Gregg RG Molecular characterization of the gene encoding the subunit of the human skeletal muscle 1,4-dihydropyridine-sensitive Ca2+ channel (CACNLG), cDNA sequence, gene structure, and chromosomal location. J Biol Chem 1993; 268: 9275–9.PubMedGoogle Scholar
  46. 46.
    McCleskey PW, Fox AP, Peldman DH, et al. Conotoxin: direct and persistent blockade of specific types of calcium channels in neurons but not muscle. Proc Natl Acad Sci USA 1987; 84: 4327–31.PubMedCrossRefGoogle Scholar
  47. 47.
    Vaughan Williams PM. Relevance of cellular to clinical electrophysiology in interpreting antiarrhythmic drug action. Am J Cardiol 1989; 64: 5J-9J.CrossRefGoogle Scholar
  48. 48.
    Huber I, Wappl E, Herzog A, et al. Conserved Ca2+-antagonist-binding properties and putative folding structure of a recombinant high-affinity dihydropy-ridines-binding domain. Biochem J 2000; 347: 829–36.PubMedCrossRefGoogle Scholar
  49. 49.
    Striessnig J, Grabner M, Mitterdorfer J, Hering S, Sinnegger MJ, Glossmann H Structural basis of drug binding to L Ca2+ channels. Trends Pharmacol Sci 1998; 19: 108–15.PubMedCrossRefGoogle Scholar
  50. 50.
    Trautwein W, Pelzer D, McDonald TF. Interval and voltage-dependent effects of the calcium channel-blocking agents D600 and AQA 39 on mammalian ventricular muscle. Circ Res 1983; 52(suppl. I): 60–8.Google Scholar
  51. 51.
    Motoike HK, Bodi I, Nakayama H, Schwartz A, Veradi G A region in IVS5 of the human cardiac L-type calcium channel is required for the use-dependent block by phenylalkylamines and benzothiazepines. J Biol Chem 1999; 274: 9409–20.PubMedCrossRefGoogle Scholar
  52. 52.
    Furukawa T, Nukada T, Suzuki K, et al. Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol 1997; 121: 1136–40.PubMedCrossRefGoogle Scholar
  53. 53.
    Fujii S, Kameyama K, Hosono M, Hayashi T, Kitamura K Effect of cilnidipine, a novel dihydropy-ridines Ca++-channel antagonist, on N-type Ca++ channel in rat dorsal root ganglion neurons. J Pharmacol Exp Ther 1997; 280: 1184–91.PubMedGoogle Scholar
  54. 54.
    Masumiya H, Shijuku T, Tanaka H, Shigenobu K Inhibition of myocardial L and T-type Ca2+ currents by efonidipine: possible mechanism for its chronotropic effect. Eur J Pharmacol 1998; 349: 351–7.PubMedCrossRefGoogle Scholar
  55. 55.
    Ritchie DM, Kirchner T, Moore JB, et al. Experimental antiasthmatic activity of RWJ 22108: a bronchoselective calcium entry blocker. Int Arch Allergy Immunol 1993; 100: 274–82.PubMedGoogle Scholar
  56. 56.
    Tamakage M, Hirshman CA, Namiki A, Croxton CA Inhibition of voltage-dependent Ca2+ channels of porcine tracheal smooth muscle by the novel Ca2+ channel antagonist RWJ-22108. Gen Pharmac 1997; 28: 689–94.Google Scholar
  57. 57.
    Bechern M, Schramm M Calcium-agonists. J Mol Cell Cardiol 1987; 19(Suppl. II): 63–75.Google Scholar
  58. 58.
    Hirning LD, Fox AP, McCleskey EW, et al. Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons. Science 1988; 239: 57–61.PubMedCrossRefGoogle Scholar
  59. 59.
    Plummer MR, Logothetic DE, Hess P. Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons. Neuron 1989; 2: 1453–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Aosaki T, Kasai H Characterization of two kinds of high-voltage-activated Ca-channel currents in chick sensory neurons. Differential sensitivity to dihydropy-ridines and -conotoxin GVIA. Pflügers Arch 1989; 414: 150–6.PubMedCrossRefGoogle Scholar
  61. 61.
    Clozel JP, Ertel EA, Ertel SI. Voltage-gated T-type Ca2+ channels and heart failure. Proc Assoc Am Physician 1999; 111: 429–37.Google Scholar
  62. 62.
    Ptàek LJ, Tawil R, Griggs RC, et al. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 1994; 77: 863–8.CrossRefGoogle Scholar
  63. 63.
    Ophoff RA, Terwindt GM, L’ergouwe MN, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996; 87: 543–52.PubMedCrossRefGoogle Scholar
  64. 64.
    Hess EJ. Migraines in mice? Cell 1996; 87: 1149–51.PubMedCrossRefGoogle Scholar
  65. 65.
    Zhuchenko O, Bailey J, Bonnen P, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha lA-voltage-dependent calcium channel. Nat Genet 1997; 15: 62–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Lennon VA, Kryzer TJ, Griesmann GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med 1995; 332: 1467–74.PubMedCrossRefGoogle Scholar
  67. 67.
    Iles DE, Lehmann-Horn F, Scherer SW, et al. Localization of the gene encoding the α2/□ -subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. Hum Mol Genet 1994; 3: 969–75.PubMedCrossRefGoogle Scholar
  68. 68.
    Rollman JE, Dickson CM. Anesthetic management of a patient with hypokalemic familial periodic paralysis for coronary artery bypass surgery. Anesthesiology 1985; 63: 526–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Robinson JE, Morin VI, Douglas MJ, Wilson RD Familial hypokalemic periodic paralysis and Wolff-Parkinson-White syndrome in pregnancy. Can J Anesth 2000; 47: 160–4.PubMedGoogle Scholar
  70. 70.
    Wise RP. A myasthenia syndrome complicating bronchial carcinoma. Anaesthesia 1962; 17: 488–90.PubMedCrossRefGoogle Scholar
  71. 71.
    Agoston S, van Weerden T, Westra P, Broekert A Effects of 4-aminopyridine in Eaton Lambert syndrome. Br J Anaesth 1978; 50: 383–5.PubMedCrossRefGoogle Scholar
  72. 72.
    Levitt RC Prospects for the diagnosis of malignant hyperthermia susceptibility using molecular genetic approaches. Anesthesiology 1992; 76: 1039–48.PubMedGoogle Scholar
  73. 73.
    Lynch C III,Vogel S, Sperelakis N Halothane depression of myocardial slow action potential. Anesthesiology 1981; 55: 360–8.PubMedGoogle Scholar
  74. 74.
    Nakao S, Hirata H, Kagawa Y. Effects of volatile anesthetics on cardiac calcium channels. Acta Anaesthesiol Scand 1989; 33: 326–30.PubMedCrossRefGoogle Scholar
  75. 75.
    Ikemoto Y, Tatani A, Arimura H, Toshitake J. Reduction of the slow inward current of isolated rat ventricular cells by thiamylal and halothane. Acta Anaesthesiol Scand 1985; 29: 583–6.PubMedGoogle Scholar
  76. 76.
    Ferrar DA, Victory JGG Isoflurane depresses membrane currents associated with contraction in myocytes isolated from guinea-pig ventricle. Anesthesiology 1988; 69: 742–9.CrossRefGoogle Scholar
  77. 77.
    Eskinder H, Kusch NJ, Supan FD, Kampine JP, Bosnjak ZJ. The effects of volatile anesthetics on L and T-type calcium channel currents in canine cardiac Purkinje cells. Anesthesiology 1991; 74: 919–26.PubMedCrossRefGoogle Scholar
  78. 78.
    Bosnjak ZJ, Supan FD, Rusch NJ. The effects of halothane, enflurane, and isoflurane on calcium current in isolated canine ventricular cells. Anesthesiology 1991; 74: 340–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Herrington J, Stern RC, Evers AS, Lingle CJ Halothane inhibits two components of calcium current in clonal (GH3) pituitary cells. J Neurosci 1991; 11: 2226–40.PubMedGoogle Scholar
  80. 80.
    Fakenoshita M, Steinbach JH. Halothane blocks low-voltage-activated calcium current in rat sensory neurons. J Neurosci 1991; 11: 1404–12.Google Scholar
  81. 81.
    McDowell FS, Pancrazio JJ, Lynch IIIC Volatile anesthetics reduce low-voltage-activated calcium currents in a thyroid C-cell line. Anesthesiology 1996; 85: 1167–75.PubMedCrossRefGoogle Scholar
  82. 82.
    Tamakage M, Hirshman CA, Croxton FL. Vlatile anesthetics inhibit voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells. Am J Physiol 1995; 268: L187–91.Google Scholar
  83. 83.
    Nikonorov IM, Blanck FJJ, Recio -Pinto E. The effects of halothane on single human neuronal L-type calcium channels. Anesth Analg 1998; 86: 885–95.PubMedCrossRefGoogle Scholar
  84. 84.
    Tamakage M, Chen X, Fsujiguchi N, Kamada T, Namiki A Different inhibitory effects of volatile anesthetics on T and L-type voltage-dependent Ca2+ channels in porcine tracheal and bronchial smooth muscles. Anesthesiology 2001; 94: 683–93.CrossRefGoogle Scholar
  85. 85.
    Hall AC, Lieb WR, Franks NP. Insensitivity of P-type calcium channels to inhalational and intravenous general anesthetics. Anesthesiology 1994; 81: 117–23.PubMedCrossRefGoogle Scholar
  86. 86.
    Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367: 607–14.PubMedCrossRefGoogle Scholar
  87. 87.
    Ferrar DA Structure and function of calcium channels and the actions of anaesthetics. Br J Anaesth 1993; 71: 39–46.CrossRefGoogle Scholar
  88. 88.
    Downie DL, Hall AC, Lieb WR, Franks NP. Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes. Br J Pharmacol 1996; 118: 493–502.PubMedGoogle Scholar
  89. 89.
    Mihic SJ, Ye Q Wick MJ, et al. Sites of alcohol and volatile anaesthetic action on GABAa and glycine receptors. Nature 1997; 389: 385–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Olcese R, Usai C, Maestrone E, Nobile M The general anesthetic propofol inhibits transmembrane calcium current in chick sensory neurons. Anesth Analg 1994; 78: 955–60.PubMedCrossRefGoogle Scholar
  91. 91.
    Baum VC, Wetzel GF, Klitzner FS. Effects of halothane and ketamine on activation and inactivation of myocardial calcium current. J Cardiovasc Pharmacol 1994; 23: 799–805.PubMedCrossRefGoogle Scholar
  92. 92.
    Yamakage M, Hirshman CA, Croxton TL. Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells. Anesthesiology 1995; 83: 1274–82.PubMedCrossRefGoogle Scholar
  93. 93.
    Hevers W, Luddens H The diversity of GABAa receptors. Pharmacological and electrophysiological properties of GABAa channel subtypes. Mol Neurobiol 1998; 18: 35–86.PubMedCrossRefGoogle Scholar
  94. 94.
    French JF, Rapoport RM, Matlib MA Possible mechanism of benzodiazepine-induced relaxation of vascular smooth muscle. J Cardiovasc Pharmacol 1989; 14: 405–11.PubMedCrossRefGoogle Scholar
  95. 95.
    Koga Y, Sato S, Sodeyama N, et al. Comparison of the relaxant effects of diazepam, flunitrazepam and midazolam on airway smooth muscle. Br J Anaesth 1992; 69: 65–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Gershon E. Effect of benzodiazepine ligands on Ca2+ channel currents in Xenopus oocytes injected with rat heart RNA. J Basic Clin Physiol Pharmacol 1992; 3: 81–97.PubMedGoogle Scholar
  97. 97.
    Buljubasic N, Marijic J, Berczi V, Supan DF, Kampine JP, Bosnjak ZJ. Differential effects of etomidate, propofol, and midazolam on calcium and potassium channel currents in canine myocardial cells. Anesthesiology 1996; 85: 1092–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Yamakage M, Matsuzaki F, Fsujiguchi N, Honma Y, Namiki A Inhibitory effects of diazepam and midazolam on Ca2+ and K+ channels in canine tracheal smooth muscle cells. Anesthesiology 1999; 90: 197–207.PubMedCrossRefGoogle Scholar
  99. 99.
    Yoshida H, Fsunoda Y, Owyang C Diazepam-binding inhibitor33 50 elicits Ca2+ oscillation and CCK secretion in STC-1 cells via L-type Ca2+ channels. Am J Physiol 1999; 276: G694–702.PubMedGoogle Scholar
  100. 100.
    Ishizawa Y, Furuya K, Yamagishi S, Dohi S. Non-GABAergic effects of midazolam, diazepam and flumazenil on voltage-dependent ion currents in NG108-15 cells. Neuroreport 1997; 8: 2635–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Butterworth JF, Strichartz GR Molecular mechanisms of local anesthesia: a review. Anesthesiology 1990; 72: 711–34.PubMedCrossRefGoogle Scholar
  102. 102.
    Akaike N, Ito H, Nishi K, Oyama Y. Further analysis of inhibitory effects of propranolol and local anaesthetics on the calcium current in Helix neurones. Br J Pharmacol 1982; 76: 37–430.PubMedGoogle Scholar
  103. 103.
    Oyama T, Sadoshima J-I, Tokutomi N, Akaike N Some properties of inhibitory action of lidocaine on the Ca2+ current of single isolated frog sensory neurons, Brain Res 1988; 442: 223–8.Google Scholar
  104. 104.
    Josephson IR Lidocaine blocks Na, Ca and K currents of chick ventricular myocytes. J Mol Cell Cardiol 1988; 20: 593–604.PubMedCrossRefGoogle Scholar
  105. 105.
    Carmeliet E, Morad M, Van der Heyden G, Vereecke J. Electrophysiological effects of tetracaine in single guinea-pig ventricular myocytes. J Physiol (Lond) 1986; 376: 143–61.Google Scholar
  106. 106.
    Kossner KL, Freese KJ. Bupivacaine inhibition of L-type calcium current in ventricular cardiomyocytes of hamster. Anesthesiology 1997; 87: 926–34.CrossRefGoogle Scholar
  107. 107.
    de La Coussaye JE, Bassoul B, Albat B, et al. Experimental evidence in favor of role of intracellular actions of bupivacaine in myocardial depression. Anesth Analg 1992; 74: 698–702.Google Scholar

Copyright information

© Canadian Anesthesiologists 2002

Authors and Affiliations

  1. 1.Department of AnesthesiologySapporo Medical University School of MedicineSapporo, HokkaidoJapan

Personalised recommendations