Role of Na(+)-H(+) exchange in the modulation of L-type Ca(2+) current during fluid pressure in rat ventricular myocytes.

Application of fluid pressure (FP) using pressurized fluid flow suppresses the L-type Ca(2+) current through both enhancement of Ca(2+) release and intracellular acidosis in ventricular myocytes. As FP-induced intracellular acidosis is more severe during the inhibition of Na(+)-H(+) exchange (NHE), we examined the possible role of NHE in the regulation of I(Ca) during FP exposure using HOE642 (cariporide), a specific NHE inhibitor. A flow of pressurized (~16 dyn/cm(2)) fluid was applied onto single rat ventricular myocytes, and the I(Ca) was monitored using a whole-cell patch-clamp under HEPES-buffered conditions. In cells pre-exposed to FP, additional treatment with HOE642 dose-dependently suppressed the I(Ca) (IC(50) = 0.97 ± 0.12 μM) without altering current-voltage relationships and inactivation time constants. In contrast, the I(Ca) in control cells was not altered by HOE642. The HOE642 induced a left shift in the steady-state inactivation curve. The suppressive effect of HOE642 on the I(Ca) under FP was not altered by intracellular high Ca(2+) buffering. Replacement of external Cl(-) with aspartate to inhibit the Cl(-)-dependent acid loader eliminated the inhibitory effect of HOE642 on I(Ca). These results suggest that NHE may attenuate FP-induced I(Ca) suppression by preventing intracellular H(+) accumulation in rat ventricular myocytes and that NHE activity may not be involved in the Ca(2+)-dependent inhibition of the I(Ca) during FP exposure.