Heterogeneity of the SR-dependent Inward Na<SUP>&#8290;</SUP>-Ca<SUP>2&#8290;</SUP> Exchange Current in the Heavily Ca<SUP>2&#8290;</SUP>-buffered Rat Ventricular Myocytes

Heterogeneity of the SR-dependent Inward Na<SUP>&#8290;</SUP>-Ca<SUP>2&#8290;</SUP> Exchange Current in the Heavily Ca<SUP>2&#8290;</SUP>-buffered Rat Ventricular Myocytes

Voltage-sensitive release mechanism was pharmacologically dissected from the Ca<SUP>2&#8290;</SUP>-induced Ca<SUP>2&#8290;</SUP> release in the SR Ca<SUP>2&#8290;</SUP> release in the rat ventricular myocytes patch-clamped in a whole-cell mode. SR Ca<SUP>2&#8290;</SUP> release process was monitored by using forward-mode Na<SUP>&#8290;</SUP>-Ca<SUP>2&#8290;</SUP> exchange after restriction of the interactions between Ca<SUP>2&#8290;</SUP> from SR and Na<SUP>&#8290;</SUP>-Ca<SUP>2&#8290;</SUP> exchange within micro-domains with heavy cytosolic Ca<SUP>2&#8290;</SUP> buffering with 10 mM BAPTA. During stimulation every 10 s with a pulse roughly mimicking action potential, the initial outward current gradually turned into a huge inward current of &#8291;12.9&#8273;0.5 pA/pF. From the inward current, two different inward I<SUB>NCX</SUB>s were identified. One was 10 μM ryanodine-sensitive, constituting 14.2&#8273;2.3%. It was completely blocked by CdCl<SUB>2</SUB> (0.1 mM and 0.5 mM) and by Na<SUP>&#8290;</SUP>-depletion. The other was identified by 5 mM NiCl<SUB>2</SUB> after suppression of I<SUB>CaL</SUB> and ryanodine receptor, constituting 14.8&#8273;1.6%. This latter was blocked by either 10 mM caffeine-induced SR Ca<SUP>2&#8290;</SUP>-depletion or 1 mM tetracaine. IV-relationships illustrated that the latter was activated until the peak in 30∼35 mV lower voltages than the former. Overall, it was concluded that the SR Ca<SUP>2&#8290;</SUP> release process in the rat ventricular myocytes is mediated by the voltage-sensitive release mechanism in addition to the Ca<SUP>2&#8290;</SUP>-induced-Ca<SUP>2&#8290;</SUP> release.