Application of fluid pressure (FP) using pressurized fluid flow suppresses the L-type Ca2+ current through both enhancement of Ca2+ 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 (similar to 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 (IC50 = 0.97 +/- 0.12 mu M) 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 Ca2+ 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 intracellularl-H+ accumulation in rat ventricular myocytes and that NHE activity may not be involved in the Ca2+-dependent inhibition of the I-Ca during FP exposure. (C) 2013 Elsevier Inc. All rights reserved.