Gokina N I, Bevan J A
Department of Pharmacology, College of Medicine, The University of Vermont, Burlington 05405, USA.
Am J Physiol Heart Circ Physiol. 2000 Jun;278(6):H2094-104. doi: 10.1152/ajpheart.2000.278.6.H2094.
The role of membrane depolarization in the histamine-induced contraction of the rabbit middle cerebral artery was examined by simultaneous measurements of membrane potential and isometric force. Histamine (1-100 microM) induced a concentration-dependent sustained contraction associated with sustained depolarization. Action potentials were observed during depolarization caused by histamine but not by high-K(+) solution. K(+)-induced contraction was much smaller than sustained contraction associated with the same depolarization caused by histamine. Nifedipine attenuates histamine-induced sustained contraction by 80%, with no effect on depolarization. Inhibition of nonselective cation channels with Co(2+) (100-200 microM) reversed the histamine-induced depolarization and relaxed the arteries but induced only a minor change in K(+)-induced contraction. In the presence of Co(2+) and in low-Na(+) solution, histamine-evoked depolarization and contraction were transient. We conclude that nonselective cation channels contribute to histamine-induced sustained depolarization, which stimulates Ca(2+) influx through voltage-dependent Ca(2+) channels participating in contraction. The histamine-induced depolarization, although an important and necessary mechanism, cannot fully account for sustained contraction, which may be due in part to augmentation of currents through voltage-dependent Ca(2+) channels and Ca(2+) sensitization of the contractile process.
通过同步测量膜电位和等长张力，研究了膜去极化在组胺诱导的兔大脑中动脉收缩中的作用。组胺（1 - 100微摩尔）诱导了浓度依赖性的持续性收缩，并伴有持续性去极化。在组胺引起的去极化过程中观察到动作电位，但在高钾溶液引起的去极化过程中未观察到。钾离子诱导的收缩远小于与组胺引起的相同去极化相关的持续性收缩。硝苯地平使组胺诱导的持续性收缩减弱80%，对去极化无影响。用钴离子（100 - 200微摩尔）抑制非选择性阳离子通道可逆转组胺诱导的去极化并使动脉舒张，但仅引起钾离子诱导收缩的微小变化。在存在钴离子和低钠溶液的情况下，组胺诱发的去极化和收缩是短暂的。我们得出结论，非选择性阳离子通道参与了组胺诱导的持续性去极化，后者通过参与收缩的电压依赖性钙离子通道刺激钙离子内流。组胺诱导的去极化虽然是一个重要且必要的机制，但不能完全解释持续性收缩，这可能部分归因于通过电压依赖性钙离子通道的电流增加以及收缩过程的钙离子敏感性增强。
