title: Role of Na(+)-H(+) exchange in the modulation of L-type Ca(2+) current during fluid pressure in rat ventricular myocytes.
abstract: 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.
authors: Laboratory of Physiology, College of Pharmacy, Chungnam National University, 220 Gungdong, Daejeon 305-764, South Korea. doctorkim@cnu.ac.kr
authors: Joon-Chul
authors: JC
authors: Kim
authors: Sun-Hee
authors: SH
authors: Woo
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D006146:Guanidines / Q000494:pharmacology; D006352:Heart Ventricles; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D011312:Pressure; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology; D016276:Ventricular Function
chemical_list: D020746:Calcium Channels, L-Type; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide