Wellman George C, Nathan David J, Saundry Christine M, Perez Guillermo, Bonev Adrian D, Penar Paul L, Tranmer Bruce I, Nelson Mark T
Department of Pharmacology, University of Vermont College of Medicine, Burlington, VT 05405-0068, USA.
Stroke. 2002 Mar;33(3):802-8. doi: 10.1161/hs0302.104089.
Local Ca2+ release events (Ca2+ sparks) caused by the opening of ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum have been suggested to oppose constriction in cerebral arteries through the activation of large-conductance Ca2+-activated K+ (BK) channels. We report the first identification and characterization of Ca2+ sparks and associated BK channel currents in smooth muscle cells isolated from human cerebral arteries.
Membrane currents and intracellular Ca2+ were measured with the use of the patch-clamp technique and laser scanning confocal microscopy.
Ca2+ sparks with a peak fractional fluorescence change (F/F0) of 2.02 +/- 0.04 and size of 8.2 +/- 0.5 microm2 (n=108) occurred at a frequency of approximately 1 Hz in freshly isolated, cerebral artery myocytes from humans. At a holding potential of -40 mV, the majority of, but not all, Ca2+ sparks (61 of 85 sparks) were associated with transient BK currents. Consistent with a role for Ca2+ sparks in the control of cerebral artery diameter, agents that block Ca2+ sparks (ryanodine) or BK channels (iberiotoxin) were found to contract human cerebral arteries.
This study provides evidence for local Ca2+ signaling in human arterial myocytes and suggests that these events may play an important role in control of cerebral artery diameter in humans.
肌浆网中兰尼碱敏感型Ca2+通道开放所引发的局部Ca2+释放事件（Ca2+火花），被认为可通过激活大电导Ca2+激活K+（BK）通道来对抗脑动脉收缩。我们首次鉴定并表征了从人脑动脉分离的平滑肌细胞中的Ca2+火花及相关的BK通道电流。
采用膜片钳技术和激光扫描共聚焦显微镜测量膜电流和细胞内Ca2+。
在新鲜分离的人脑动脉肌细胞中，Ca2+火花的峰值荧光分数变化（F/F0）为2.02±0.04，大小为8.2±0.5μm2（n = 108），出现频率约为1Hz。在-40mV的钳制电位下，大部分（但并非全部）Ca2+火花（85个火花中的61个）与瞬时BK电流相关。与Ca2+火花在控制脑动脉直径中所起的作用一致，发现阻断Ca2+火花的药物（兰尼碱）或BK通道的药物（iberiotoxin）会使人类脑动脉收缩。
本研究为人类动脉肌细胞中的局部Ca2+信号传导提供了证据，并表明这些事件可能在控制人类脑动脉直径中发挥重要作用。
