Suppression of L-type Ca2+ current by fluid pressure in rat ventricular myocytes: possible role of Cl(-)-OH(-) exchange.

The application of fluid pressure (FP) in ventricular myocytes using pressurized fluid flow inhibits L-type Ca(2+) current (I(Ca)), with approximately 80% of this effect coming through the enhancement of Ca(2+) releases from the sarcoplasmic reticulum. In the present study, we explored the remaining mechanisms for the inhibition of I(Ca) by FP. Since FP significantly increases H(+) concentration and H(+) is known to inhibit I(Ca), we examined whether pH regulation plays a role in the inhibitory effect by FP on I(Ca). A flow of pressurized (∼16.3 dyne/cm(2)) fluid, identical to that bathing the myocytes, was applied onto single rat ventricular myocytes for which the I(Ca) was monitored using whole-cell patch-clamp under HEPES-buffered conditions. Extracellular application of the alkalizing agent, NH(4)Cl (20 mM), enhanced I(Ca) by ∼34% in the control conditions while increasing I(Ca) significantly less (by ∼21%) in FP-pretreated myocytes, suggesting an inhibition of the effect of NH(4)Cl on I(Ca) possibly by FP-induced acidosis. Application of DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, 500μM), which blocks Cl(-)-HCO(3)(-) exchange but not Cl(-)-OH(-) exchange, did not alter the inhibitory effect of FP on I(Ca). Replacement of external Cl(-) with aspartate attenuated the inhibitory effect of FP on I(Ca). In highly Ca(2+)-buffered cells, where Ca(2+)-dependent inhibition of I(Ca) was minimized, the external Cl(-) removal eliminated the inhibitory effect of FP on I(Ca). These results suggest that the decrease of I(Ca) in the presence of FP is at least partly caused by intracellular acidosis via activation of Cl(-)-OH(-) exchange in rat ventricular myocytes.