Effects of NCX on ICa,L kinetics by the subsarcolemmal Ca²⁺ change in cardiomyocytes of pulmonary vein

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Ca²⁺ dependent inactivation of L-type Ca²⁺ is well known phenomena. In this study, we would like to see the effect of NCX on ICaL kinetics by the change of subsarcolemmal Ca²⁺. We used the isolated cardiomyocytes in main pulmonary vein of rabbit and applied the whole cell voltage clamp techniques. In the presence of 0.1 mM EGTA in pipette solution, we applied a step depolarization prepulse from -40 mV to 10 mV for 2.5 msec to induce Ca²⁺ release from SR. And then, the test pulse of the same amplitude was applied. As the interval between the prepulse and the test pulse was increased, the inactivation time constants (taus) were decreased. In the absence of extracellular Na⁺, the taus were decreased further. The peak current amplitude was decreased at the first test pulse and became increased as the interval was increased to the control level. In the absence of extracellular Na⁺, the peak current decreased much larger and it increased much slowly. In the presence of BAPTA, ryanodine or thapsigargin, these phenomena were disappeared. SEA0400, a blocker of NCX, did not inhibit Ca²⁺ currents in the presence of BAPTA 10 mM but EGTA 0.1 mM. From these results, the release of SR Ca²⁺ could induce the rapid inactivation of L-type Ca²⁺ channels. Na⁺-Ca²⁺ exchange seems to be important to modulate L-type Ca²⁺ channel amplitude and inactivation kinetics by reducing subsarcolemmal Ca²⁺. SEA0400 was donated from Taisho Pharmaceutical Co. Ltd. This work was supported by the grant (No. R01-2004-000-10374-0) from KOSEF. [J Physiol Sci. 2007;57 Suppl:S14]