백서 심방 근세포에서 전단자극에 의한 P2X 퓨린수용체의 활성화

Activation of P2X Purinoceptor by Shear Stress in Rat Atrial Myocytes

Atrial myocytes are subjected to shear stress under physiological and pathological conditions during cardiac cycle. It has been recently suggested that ATP release of atrial cells induces longitudinal Ca 2+ wave via activation of P2Y 1 purinergic signaling in rat atrial myocytes under shear stress. In the present study, we examined whether P2X purinoceptor, a non-selective cation channel, is activated in these cells using a whole-cell patch clamp combined with a pressurized microflow system. Shear stress of ~16 dyne/cm 2 (1-s long) produced a slow inward current(I SS ) at −70 mV in symmetrical CsClrich solutions. Removal of external Ca 2+ significantly enhanced the I SS by approximately 140%. Pre-treatment of suramin(10 µM), the general P2-purinoceptor antagonist, suppressed the I SS by ~70%. In addition, the I SS was inhibited by ~50% by pre-exposure to P2X purinoceptor inhibitor, iso-PPADS(100 µM). Inhibition of transient receptor potential melastatin 4, the Ca 2+ -activated non-selective cation channel, using 9-phenanthrol(30 µM) decreased I SS by ~30%. When the delayed rectifying K + channels, that have slight permeability to Cs + , were blocked using 4-aminopyridine(200 µM), I SS was not altered. Our data suggest that shear stress activates P2X purinoceptors in atrial myocytes, thereby partly contributing to shear-activated slow cation influx at resting membrane potential.