Forward-Mode Na<SUP>⁢</SUP>-Ca<SUP>2⁢</SUP> Exchange during Depolarization in the Rat Ventricular Myocytes with High EGTA
Forward-Mode Na<SUP>⁢</SUP>-Ca<SUP>2⁢</SUP> Exchange during Depolarization in the Rat Ventricular Myocytes with High EGTA
- Eun-Gi Kim Chang Mann Ko
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제5권 제6호
- 등재여부 : KCI등재
- 2001.01
- 487 - 494 (8 pages)
<P> During depolarization, extrusion of Ca<SUP>2⁢</SUP> from sarcoplasmic reticulum through forward-mode Na<SUP>⁢</SUP>-Ca<SUP>2⁢</SUP> exchange was studied in the rat ventricular myocytes patch-clamped in whole-cell configuration. In order to confine the Ca<SUP>2⁢</SUP> responses in a micro-domain by limiting the Ca<SUP>2⁢</SUP> diffusion time, rat ventricular myocytes were dialyzed with high (14 mM) EGTA. K<SUP>⁢ </SUP>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<SUP>⁣</SUP> 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 CdCl<SUB>2</SUB>. 10 mM caffeine increased the remaining inward current after CdCl<SUB>2</SUB> in a cAMP-dependent manner. This caffeine-induced inward current was blocked by 1μM ryanodine, 10μM thapsigargin, 5 mM NiCl<SUB>2</SUB>, or by Na<SUP>⁢</SUP> and Ca<SUP>2⁢</SUP> omission, but not by 0.1μM isoproterenol. The I∼V 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<SUP>⁢</SUP>-Ca<SUP>2⁢</SUP> exchange extrudes a fraction of Ca<SUP>2⁢</SUP> released from sarcoplasmic reticulum mainly by voltage-sensitive release mechanism in a micro-domain in the t-tubule, which is functionally separable from global Ca<SUP>2⁢</SUP><SUB>i</SUB> by EGTA.