Sergeant G P, Hollywood M A, McCloskey K D, McHale N G, Thornbury K D
Smooth Muscle Group, Department of Physiology, The Queen's University of Belfast, Belfast BT9 7BL, Northern Ireland, United Kingdom.
Am J Physiol Cell Physiol. 2001 May;280(5):C1349-56. doi: 10.1152/ajpcell.2001.280.5.C1349.
Isolated interstitial ("pacemaker") cells from rabbit urethra were examined using the perforated-patch technique. Under voltage clamp at -60 mV, these cells fired large spontaneous transient inward currents (STICs), averaging -860 pA and >1 s in duration, which could account for urethral pacemaker activity. Spontaneous transient outward currents (STOCs) were also observed and fell into two categories, "fast" (<100 ms in duration) and "slow" (>1 s in duration). The latter were coupled to STICs, suggesting that they shared the same mechanism, while the former occurred independently at faster rates. All of these currents were abolished by cyclopiazonic acid, caffeine, or ryanodine, suggesting that they were activated by Ca(2+) release. When D-myo-inositol 1,4,5-trisphosphate (IP(3))-sensitive stores were blocked with 2-aminoethoxydiphenyl borate, the STICs and slow STOCs were abolished, but the fast STOCs remained. In contrast, the fast STOCs were more nifedipine sensitive than the STICs or the slow STOCs. These results suggest that while fast STOCs are mediated by a mechanism similar to STOCs in smooth muscle, STICs and slow STOCs are driven by IP(3). These results support the hypothesis that pacemaker activity in the urethra is driven by the IP(3)-sensitive store.
采用穿孔膜片钳技术对兔尿道分离的间质(“起搏”)细胞进行了研究。在-60 mV电压钳制下,这些细胞产生大量自发性瞬时内向电流(STICs),平均为-860 pA,持续时间>1秒,这可能是尿道起搏活动的原因。还观察到自发性瞬时外向电流(STOCs),并分为两类,“快速”(持续时间<100毫秒)和“慢速”(持续时间>1秒)。后者与STICs相关联,表明它们具有相同的机制,而前者以更快的速率独立发生。所有这些电流都被环匹阿尼酸、咖啡因或ryanodine消除,表明它们是由Ca(2+)释放激活的。当用2-氨基乙氧基二苯基硼酸阻断D-肌醇1,4,5-三磷酸(IP(3))敏感储存库时,STICs和慢速STOCs被消除,但快速STOCs仍然存在。相反,快速STOCs比STICs或慢速STOCs对硝苯地平更敏感。这些结果表明,虽然快速STOCs是由与平滑肌中STOCs类似的机制介导的,但STICs和慢速STOCs是由IP(3)驱动的。这些结果支持了尿道起搏活动由IP(3)敏感储存库驱动的假说。