유체 압력에 의한 흰쥐 심실근세포 pH의 감소 및 Na+ -H+ 교환체의 활성화

Decrease of Intracellular pH and Activation of Na+ -H+ Exchanger by Fluid Pressure in Rat Ventricular Myocytes

An increase in ventricular pressure can alter cardiac excitation and contraction. Recent report has demonstrated that fluid pressure (FP) suppresses L-type Ca2+ current with acceleration of the current inactivation in ventricular myocytes. Since the L-type Ca2+ channels known to be regulated by intracellular pH (pHi), this study was designed to explore whether pressurized fluid flow affects pHi in isolated rat ventricular myocytes. A flow of pressurized (~16 dyne/cm2) fluid, identical to that bathing the myocytes, was applied onto single myocytes, and intracellular H+ concentration was monitored using confocal H+ imaging. FP significantly decreased pHi by 0.07±0.01 pH units (n=16, P<0.01). Intracellular acidosis enhances the activity of Na+-H+ exchanger (NHE). Therefore, we examined if the NHE activity is increased by FP using the NHE inhibitor, HOE642. Although HOE642 did not alter pHi in control conditions, it decreased pHi in cells pre-exposed to FP, suggesting enhancement of NHE activity by FP. In addition, FP-induced intracellular acidosis was larger in cells pre-treated with HOE642 than in cells under the control conditions. These results suggest that FP induces intracellular acidosis and that NHE may contribute to extrude H+ during the FP-induced acidosis in rat ventricular myocytes.