Effect of Tetrodotoxin, Lidocaine, and Quinidine on the Transient Inward Current of Sheep Purkinje Fibres

Overview

Journal Basic Res Cardiol

Specialty Cardiology & Vascular Diseases

Date 1988 Mar 1

PMID 3395315

Authors

B Henning

M Zehender

T Meinertz

H Just

Affiliations

Soon will be listed here.

Abstract

The effect of tetrodotoxin (TTX), lidocaine, and quinidine on the transient inward current (TI) was studied in voltage-clamped sheep cardiac Purkinje fibres. The TI was induced by elevation of extracellular Ca or addition of strophanthidin. Reduction of external Na had a biphasic effect on the steady state TI magnitude; a moderate (less than 50%) reduction of external Na had an enhancing effect on the TI; a further decrease of extracellular Na was accompanied by a decline of TI amplitude. The TI could not be induced in Na-free medium (external Ca less than or equal to 9.0 mM). TTX, lidocaine, and quinidine reduced the magnitude of the TI in a dose-dependent way. The blocking effect of these agents could be compensated for by a moderate (less than 50%) reduction of external Na or an elevation of extracellular Ca. It is suggested that the blocking effect of TTX, lidocaine, and quinidine on the TI is due to a reduction of intracellular Na, which causes a decay of intracellular Ca via the Na-Ca exchange mechanism.

References

TRAUTWEIN W, McDONALD T, Tripathi O . Calcium conductance and tension in mammalian ventricular muscle. Pflugers Arch. 1975; 354(1):55-74. DOI: 10.1007/BF00584503. View

Kass R, Lederer W, Tsien R, Weingart R . Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978; 281:187-208. PMC: 1282691. DOI: 10.1113/jphysiol.1978.sp012416. View

Ferrier G, MOE G . Effect of calcium on acetylstrophanthidin-induced transient depolarizations in canine Purkinje tissue. Circ Res. 1973; 33(5):508-15. DOI: 10.1161/01.res.33.5.508. View

Arlock P, KATZUNG B . Effects of sodium substitutes on transient inward current and tension in guinea-pig and ferret papillary muscle. J Physiol. 1985; 360:105-20. PMC: 1193450. DOI: 10.1113/jphysiol.1985.sp015606. View

Batra S . The effects of drugs on calcium uptake and calcium release by mitochondria and sarcoplasmic reticulum of frog skeletal muscle. Biochem Pharmacol. 1974; 23(1):89-101. DOI: 10.1016/0006-2952(74)90316-5. View

Kass R, Tsien R, Weingart R . Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978; 281:209-26. PMC: 1282692. DOI: 10.1113/jphysiol.1978.sp012417. View

Sheu S, Fozzard H . Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development. J Gen Physiol. 1982; 80(3):325-51. PMC: 2228682. DOI: 10.1085/jgp.80.3.325. View

Lederer W, Tsien R . Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J Physiol. 1976; 263(2):73-100. PMC: 1307691. DOI: 10.1113/jphysiol.1976.sp011622. View

Colquhoun D, Neher E, Reuter H, Stevens C . Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature. 1981; 294(5843):752-4. DOI: 10.1038/294752a0. View

10.

Reuter H, Seitz N . The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol. 1968; 195(2):451-70. PMC: 1351672. DOI: 10.1113/jphysiol.1968.sp008467. View

11.

Noble D . The surprising heart: a review of recent progress in cardiac electrophysiology. J Physiol. 1984; 353:1-50. PMC: 1193291. DOI: 10.1113/jphysiol.1984.sp015320. View

12.

Kass R, Tsien R . Fluctuations in membrane current driven by intracellular calcium in cardiac Purkinje fibers. Biophys J. 1982; 38(3):259-69. PMC: 1328867. DOI: 10.1016/S0006-3495(82)84557-8. View

13.

Haas H, Kern R, Einwachter H, TARR M . Kinetics of Na inactivation in frog atria. Pflugers Arch. 1971; 323(2):141-57. DOI: 10.1007/BF00586445. View

14.

Bianchi C, Bolton T . Action of local anesthetics on coupling systems in muscle. J Pharmacol Exp Ther. 1967; 157(2):388-405. View

15.

Saikawa T, Carmeliet E . Slow recovery of the maximal rate of rise (Vmax) of the action potential in sheep cardiac Purkinje fibers. Pflugers Arch. 1982; 394(1):90-3. DOI: 10.1007/BF01108313. View

16.

Deitmer J, Ellis D . The intracellular sodium activity of sheep heart Purkinje fibres: effects of local anaesthetics and tetrodotoxin. J Physiol. 1980; 300:269-82. PMC: 1279354. DOI: 10.1113/jphysiol.1980.sp013161. View

17.

Wasserstrom J, Ferrier G . Effects of phenytoin and quinidine on digitalis-induced oscillatory afterpotentials, aftercontractions, and inotropy in canine ventricular tissues. J Mol Cell Cardiol. 1982; 14(12):725-36. DOI: 10.1016/0022-2828(82)90185-7. View

18.

Tsien R, Kass R, Weingart R . Cellular and subcellular mechanisms of cardiac pacemaker oscillations. J Exp Biol. 1979; 81:205-15. DOI: 10.1242/jeb.81.1.205. View

19.

Eisner D, Lederer W, Sheu S . The role of intracellular sodium activity in the anti-arrhythmic action of local anaesthetics in sheep Purkinje fibres. J Physiol. 1983; 340:239-57. PMC: 1199208. DOI: 10.1113/jphysiol.1983.sp014761. View

20.

Lee K, Hume J, Giles W, Brown A . Sodium current depression by lidocaine and quinidine in isolated ventricular cells. Nature. 1981; 291(5813):325-7. DOI: 10.1038/291325a0. View