Fluid pressure modulates L-type Ca2+ channel via enhancement of Ca2+-induced Ca2+ release in rat ventricular myocytes.

This study examines whether fluid pressure (FP) modulates the L-type Ca(2+) channel in cardiomyocytes and investigates the underlying cellular mechanism(s) involved. A flow of pressurized (approximately 16 dyn/cm(2)) fluid, identical to that bathing the myocytes, was applied onto single rat ventricular myocytes using a microperfusion method. The Ca(2+) current (I(Ca)) and cytosolic Ca(2+) signals were measured using a whole cell patch-clamp and confocal imaging, respectively. It was found that the FP reversibly suppressed I(Ca) (by 25%) without altering the current-voltage relationships, and it accelerated the inactivation of I(Ca). The level of I(Ca) suppression by FP depended on the level and duration of pressure. The Ba(2+) current through the Ca(2+) channel was only slightly decreased by the FP (5%), suggesting an indirect inhibition of the Ca(2+) channel during FP stimulation. The cytosolic Ca(2+) transients and the basal Ca(2+) in field-stimulated ventricular myocytes were significantly increased by the FP. The effects of the FP on the I(Ca) and on the Ca(2+) transient were resistant to the stretch-activated channel inhibitors, GsMTx-4 and streptomycin. Dialysis of myocytes with high concentrations of BAPTA, the Ca(2+) buffer, eliminated the FP-induced acceleration of I(Ca) inactivation and reduced the inhibitory effect of the FP on I(Ca) by approximately 80%. Ryanodine and thapsigargin, abolishing sarcoplasmic reticulum Ca(2+) release, eliminated the accelerating effect of FP on the I(Ca) inactivation, and they reduced the inhibitory effect of FP on the I(Ca). These results suggest that the fluid pressure indirectly suppresses the Ca(2+) channel by enhancing the Ca(2+)-induced intracellular Ca(2+) release in rat ventricular myocytes.