Advertisement

Evidence for a Modulated Receptor Mechanism of Calcium Channel Blockade

  • C. W. Clarkson
  • M. Inazawa
  • S. Kanaya
  • L. M. Hondeghem
  • B. G. Katzung
Chapter
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 39)

Abstract

A large body of evidence suggests that the action of local anesthetics and antiarrhythmic drugs on membrane sodium channels is modulated by the state of the channel. That is, the affinity of the drug for its receptor varies and depends on whether the channel is rested and available, activated and open (conducting), or closed and inactivated (1–4) (see Fig. 1). The modulated receptor hypothesis for the action of sodium channel blockers has provided explanations for such phenomena as the selective depression of conduction in ischemic myocardium, suppression of tachycardias, and the selective action of lidocaine on ventricular vs. atrial tissue (4).

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hille B: Local anesthetics: Hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol (69): 497–515, 1977.PubMedCrossRefGoogle Scholar
  2. 2.
    Hondeghem LM, Katzung BG: Time- and voltage-dependent interactions of antiarrhythmic drugs with cardiac sodium channels. Biochim Biophys Acta (472): 373–398, 1977.PubMedCrossRefGoogle Scholar
  3. 3.
    Hondeghem LM, Katzung BG: Test of a model of antiarrhythmic drug action. Effect of quinidine and lidocaine on myocardial conduction. Circulation (61): 1217–1224, 1980.PubMedCrossRefGoogle Scholar
  4. 4.
    Hondeghem LM, Katzung BG: Antiarrhythmic agents: Modulated receptor mechanism of action of sodium and calcium channel blocking drugs. Annual Rev Pharmacol (in press), 1984.Google Scholar
  5. 5.
    Kawai C, Konishi T, Matsuyama E, Ohazaki H: Comparative effects of three calcium antagonists, diltiazem, verapamil, and nifedipine, on the sinoatrial and atrioventricular nodes. Experimental and clinical studies. Circulation (63): 1035–1042, 1981.PubMedCrossRefGoogle Scholar
  6. 6.
    Trautwein W, Pelzer D, McDonald TF, Osterrieder W: AQA 39, a new bradycardic agent which blocks myocardial calcium (Ca) channels in a frequency- and voltage-dependent manner. Naunyn-Schmiedeberg’s Arch Pharmacol (317): 228–232, 1981.CrossRefGoogle Scholar
  7. 7.
    Hescheler J, Pelzer, Trube G, Trautwein W: Does the organic calcium blocker D600 act from inside or outside the cardiac cell membrane? Pflugers Arch 393: 287–291, 1982.PubMedCrossRefGoogle Scholar
  8. 8.
    Pelzer D, Trautwein W, McDonald TF: Calcium channel block and recovery from block in mammalian ventricular muscle treated with organic channel inhibitors. Pflugers Arch (394): 97–105, 1982.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee KS, Tsien RW: Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature (302): 790–794, 1983.PubMedCrossRefGoogle Scholar
  10. 10.
    Kanaya S, Arlock P, Katzung BG, Hondeghem L: Diltiazem and verapamil preferentially block inactivated calcium channels. J Mol Cell Cardiol (15): 145–148, 1983.PubMedCrossRefGoogle Scholar
  11. 11.
    Kass RS: Nisoldipine: a new, more selective calcium current blocker in cardiac Purkinje fibers. J Pharmacol Exp Therap (223): 446–456, 1982.Google Scholar
  12. 12.
    Colatsky TJ: Quinidine block of cardiac sodium channels is rate- and voltage-dependent. Biophys J (37): 343a, 1982.Google Scholar
  13. 13.
    Mason JW, Hondeghem LM, Katzung BG: Amiodarone blocks inactivated cardiac sodium channels. Pflugers Arch (396): 79–81, 1983.PubMedCrossRefGoogle Scholar
  14. 14.
    Kass RS, Scheuer T: Slow inactivation of calcium channels in the cardiac Purkinje fiber. J Mol Cell Cardiol (14): 615–618, 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    Holck M, Thorens S, Haeusler G: Characterization of [3H]nifedipine binding sites in rabbit myocardium. Eur J Pharmacol 85: 305–315, 1982.PubMedCrossRefGoogle Scholar
  16. 16.
    DePover A, Matlib MA, Lee SW, Dube GP, Grupp IL, Grupp G, Schwartz A: Specific binding of [3H]nitrendipine to membranes from coronary ar¬teries and heart in relation to pharmacological effects. Paradoxical stimulation by diltiazem. Biochem Biophys Res Comm (108): 110–117, 1982.PubMedCrossRefGoogle Scholar
  17. 17.
    Godfraind T, Dieu D: The inhibition by flunarizine of the norepineph- rine-evoked contraction and calcium influx in rat aorta and mesenteric arteries. J Pharmacol Exp Therap (217): 510–515, 1981.Google Scholar
  18. 18.
    Jones AW: Vascular smooth muscle and alterations during hypertension. In: Bulbring E, Brading AF, Jones AW, Tomita T (eds) Smooth muscle: an assessment of current knowledge. University of Texas Press, Austin, 1981, pp 397–430.Google Scholar
  19. 19.
    Clusin WT, Bristow MR, Bain DS, Schroeder JS, Jaillon P, Brett P, Harrison DC: The effects of diltiazem and reduced serum calcium on is-chemic ventricular fibrillation in the dog. Circ Res (50): 518–526, 1982.PubMedCrossRefGoogle Scholar
  20. 20.
    Weishaar RE, Bing RJ: The beneficial effect of a calcium channel blocker diltiazem, on the ischemic-reperfused heart. J Mol Cell ardiol (12): 993–1009, 1980.CrossRefGoogle Scholar
  21. 21.
    Bush LR, Romson JL, Ash JL, Lucchesi BR: Effects of diltiazem on extent of ultimate myocardial injury resulting from temporary coronary artery occlusion in dogs. J Cardiovasc Pharmacol (4): 285–296, 1982.PubMedCrossRefGoogle Scholar
  22. 22.
    Clusin WT, Bristow MR, Karagueuzian HS, Katzung BG, Schroeder JS: Do calcium-dependent ionic currents mediate ischemic ventricular fibrillation? Am J Cardiol (49): 606–612, 1982.PubMedCrossRefGoogle Scholar
  23. 23.
    El-Sherif N, Lazzara R: Reentrant ventricular arrhythmias in the late myocardial infarction period. Effect of verapamil and D600 and the role of the “slow channel”. Circulation (60): 605–615, 1979.PubMedCrossRefGoogle Scholar
  24. 24.
    Yamaguchi I, Obayashi K, Mandel WJ: Electrophysiological effects of verapamil. Cardivasc Res (12): 597–608, 1982.CrossRefGoogle Scholar
  25. 25.
    Sheehan FH, Epstein SE: Effects of calcium channel blocking agents on reperfusion arrhythmias. Am Heart J (103): 973–977, 1982.PubMedCrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1984

Authors and Affiliations

  • C. W. Clarkson
    • 1
  • M. Inazawa
    • 1
  • S. Kanaya
    • 1
  • L. M. Hondeghem
    • 1
  • B. G. Katzung
    • 1
  1. 1.Department of PharmacologyUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations