Fluid Pressure-Gated Cation Channel in Atrial Myocytes

Abstract

Regurgitant jets of blood in patients with mitral valve incompetence are known to predispose to atrial fibrillation. To understand cellular basis for the fibrillation induced by the fluid jet, we examined ionic currents induced by a fluid pressure (FP) in rat atrial myocytes. FP was applied by pressurized rapid (∼15 dyne/cm2) puffing of bathing solutions onto whole-cell clamped single atrial myocytes. Puffing (1-s long) of normal external solution produced inward current (IFP) at a resting membrane potential, which was inactivated independently of FP. The current-voltage relationship of IFP showed inward rectification with a reversal potential of ≈-18 mV. Ca2+-free extracellular solution enhanced IFP by ≈7-fold and eliminated the inactivation of IFP. IFP was decreased by extracellular divalent cations with the strongest suppression by Ca2+ (Ca2+ > Cd2+ > Ni2+). Removal of extracellular K+ or Na+ decreased IFP by ≈46% or ≈35%, respectively. IFP was almost completely suppressed in K+- and Na+-free extracellular solution. Increase of extracellular Ca2+ concentration to 75 mM enhanced IFP, indicating contribution of Ca2+ to IFP. IFP was resistant to the blockade of the stretch-activated channel or Na+-Ca2+ exchanger. Intracellular Ca2+ buffering with 4 mM EGTA did not alter the magnitude and inactivation of IFP. IFP was increased to ≈200% immediately after a depletion of Ca2+ in the sarcoplasmic reticulum using 10 mM caffeine. Our data provide functional evidence for a novel inwardly rectifying nonselective cation channel in rat atrial myocytes that is gated by fluid pressure. This channel appears to be inactivated by external Ca2+-dependent mechanism and accelerated by depletion of the Ca2+ store. The FP-dependent cation influx at resting potential may be a possible mechanism for the blood-jet induced atrial fibrillation in mitral valve incompetence.