Fluid Pressure-Activated Non-Selective Cation Current and Cl- Current in Rat Atrial Myocytes

Abstract

When intact atrial muscle is exposed to turbulant flow or high fluid pressure during valve diseases, it produces arrhythmias. Here we characterized a novel fluid pressure (FP)-gated ionic current (IFP) in single rat atrial myocytes using a whole-cell patch clamp. A flow of pressurized (∼16 dyn/cm2) fluid was applied onto single rat atrial myocytes using a microperfusion method. The application of FP with a normal bath solution elicited a transient inward current (∼1 pA/pF at −80 mV). The magnitude of IFP was increased in a pressure-dependent manner. The removal of extracellular Ca2+ largely enhanced the IFP and eliminated the current adaptation. Under physiological ionic gradients, the IFP displayed an inwardly- and outwardly-rectifying current-voltage relationship with a reversal potential (Erev) of approximately −52 mV. The Cl− channel blockers, DIDS and 9-AC, suppressed inward and outward IFP by about 50% and 70-80%, respectively. In symmetrical Cl− solutions, the Erev was shifted rightward (≌−18 mV) and the outwardly rectifying IFP was attenuated. In the symmetrical Cl− conditions, removal of extracellular Na+ largely reduced inward IFP, and produced a left shift of Erev (≌−64 mV). In addition, the elimination of internal K+ shifted Erev to ≌+8.4 mV and decreased outward IFP. Although low concentrations of extracellular Ca2+ blocked IFP with a negative shift of Erev, high concentrations of extracellular Ca2+ produced a right shift of Erev. Gadolinium ion (Gd3+), the stretch-activated channel blocker, partially blocked the inward IFP. In current-clamped cells, FP of the same magnitude elicited spontaneous membrane depolarization with repetitive action potentials and prolonged action potential durations. These results indicate that FP may activate an outwardly rectifying Cl− channel and a Gd3+- and Ca2+-sensitive non-selective cation channel that carries Na+, K+, and Ca2+.