Forward-mode Na+ - Ca2+ exchange during depolarization in the rat ventricular myocytes with high EGTA.
- Author:
Eun Gi KIM
1
;
Chang Mann KO
Author Information
1. Department of Pharmacology, Yonsei University Wonju-College of Medicine, 162 Ilsan-dong, Wonju, 220-701, Korea. Changmko@Wonju.Yonsei.Ac.Kr
- Publication Type:Original Article
- MeSH:
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid;
Action Potentials;
Animals;
Cadmium Chloride;
Caffeine;
Diffusion;
Egtazic Acid*;
Isoproterenol;
Muscle Cells*;
Rats*;
Ryanodine;
Sarcoplasmic Reticulum;
Tea;
Thapsigargin
- From:The Korean Journal of Physiology and Pharmacology
2001;5(6):487-494
- CountryRepublic of Korea
- Language:English
-
Abstract:
During depolarization, extrusion of Ca2+ from sarcoplasmic reticulum through forward-mode Na+ - Ca2+ exchange was studied in the rat ventricular myocytes patch-clamped in whole-cell configuration. In order to confine the Ca2+ responses in a micro-domain by limiting the Ca2+ diffusion time, rat ventricular myocytes were dialyzed with high (14 mM) EGTA. K+ current was suppressed by substituting KCl with 105 mM CsCl and 20 mM TEA in the pipette filling solution and by omitting KCl in the external Tyrode solution. Cl- current was suppressed by adding 0.1 mM DIDS in the external Tyrode solution. During stimulation roughly mimicking action potential, the initial outward current was converted into inward current, 47+/-1% of which was suppressed by 0.1 mM CdCl2. 10 mM caffeine increased the remaining inward current after CdCl2 in a cAMP-dependent manner. This caffeine-induced inward current was blocked by 1 muM ryanodine, 10 muM thapsigargin, 5 mM NiCl2, or by Na+ and Ca2+ omission, but not by 0.1 muM isoproterenol. The IapprxV relationship of the caffeine-induced current elicited inward current from -45 mV to +3 mV with the peak at -25 mV. Taken together, it is concluded that, during activation of the rat ventricular myocyte, forward-mode Na+ - Ca2+ exchange extrudes a fraction of Ca2+ released from sarcoplasmic reticulum mainly by voltage-sensitive release mechanism in a micro-domain in the t-tubule, which is functionally separable from global Cai2+ by EGTA.
