전단 자극 시 심방근세포 간극접합 채널 활성화에 의한 P2 퓨린수용체-매개 비선택성 양이온 전류의 발생 = Generation of P2 Purinoceptor-Mediated Nonselective Cation Current by Activation of Gap-Junction Hemichannels in Atrial Myocytes under Shear Stress

다국어 초록 (Multilingual Abstract)

Atrial myocytes are subjected to shear stress under physiological and pathological conditions during cardiac cycle. We recently reported that gap junction hemichannels play a role in the generation of Ca2+ wave in atrial cells under shear stress. In the present study, we examined whether ionic current is generated by the activation of gap junction hemichannels in rat atrial myocytes under shear stress using whole-cell patch clamp method combined with a pressurized microflow system. Shear stress of ~16 dyne/cm2 (1-s long) produced a slow inward current (ISS) at –70 mV in symmetrical CsCl-rich solutions.Removal of external Ca2+ to enhance hemichannel opening increased this shear-activated current by approximately 140%. In addition, the ISS was almost completely inhibited by the hemichannel blockers carbenoxolone (50 μM) or La3+ (2 mM). We next tested whether P2 purinoceptors activated by ATP released via hemichannels contribute to ISS cells using P2-purinoceptor antagonist suramin. Pre-treatment of suramin (10 μM) suppressed ISS to ~28% of control. When the delayed rectifying K+ channels, that have slight permeability to Cs+, were blocked using 4-aminopyridine (200 μM), ISS was not altered. Our data suggest that shear stress may activate gap-junction hemichannels, resulting in ATP release with subsequent P2 purinoceptor-mediated nonselective cation current in atrial myocytes.