Dihydropyridine inhibition of single calcium channels and contraction in rabbit mesenteric artery depends on voltage.
Dihydropyridine inhibition of single calcium channels and contraction in rabbit mesenteric artery depends on voltage.
复制标题
二氢吡啶对单一钙通道的抑制作用和兔肠系膜动脉的收缩取决于电压。
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发表时间：
1989
期刊：
影响因子：
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通讯作者：
J. Worley
中科院分区：
文献类型：
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作者：
M. Nelson;J. Worley
1.在家兔肠系膜动脉中，检测了Bay K 8644存在下膜电位和二氢吡啶类钙通道抑制剂尼索地平对单钙通道的影响以及Bay K 8644存在和不存在下收缩的影响。2.膜去极化降低了可由测试脉冲引起的峰值平均单钙通道电流至0 mV。稳态失活关系可用Boltzmann方程[1 + exp[Vm-V0.5）/k）]-1描述，陡度因子k为7.1 mV。尼索地平通过增加无开口的试验脉冲分数，使稳态失活曲线向更负的电位移动。3.尼索地平对平均单钙通道电流的抑制程度随膜去极化而增加。在存在1 μ M Bay K 8644的情况下，将保持电位从-100 mV去极化至-55 mV，使50%抑制所需的尼索地平浓度（Kapp）从12.1 nM降至1.9 nM。4.在尼索地平存在下，完整动脉的外部钾（K+）的膜去极化降低了去极化测试脉冲引起的收缩。膜电位和收缩之间的关系可以通过Boltzmann方程经验性地描述，陡度因子k为7.1 mV。将尼索地平浓度从0.25 nM增加至2.0 nM，使该关系的中点从-20.5 mV移动至-33.0 mV，而不影响陡度因子。5.尼索地平的收缩抑制作用随膜去极化而增强。膜去极化从-68.6 mV降至-30.0 mV，尼索地平收缩的Kapp从3.02 nM降至0.69 nM。Bay K 8644（1 μ M）在5 mM-K+下使Kapp升高约9.3倍。在Bay K 8644存在下，膜去极化从-68.6 mV降至-30.0 mV，Kapp从28.4 nM降至4.0 nM。6.在尼索地平的存在下，膜去极化对抑制发展的时间过程的影响进行了检查。在3 nM尼索地平中，在用20 mM-K+进行膜去极化后，力抑制的发展时间过程可以用时间常数为16.5 min的单指数来描述。膜去极化至更正的电位加速了抑制的发展。7.结果被解释的模型中，尼索地平结合更高的亲和力，比静息状态的钙通道在肠系膜动脉的失活状态。本文提出的方法可用于估计生理条件下完整动脉中平滑肌细胞稳态钙通道失活和二氢吡啶相互作用的性质。（400字处截断摘要）
1. The effects of membrane potential and the dihydropyridine calcium channel inhibitor, nisoldipine, on single calcium channels in the presence of Bay K 8644 and contraction in the presence and absence of Bay K 8644 were examined in the rabbit mesenteric artery. 2. Membrane depolarization decreased the peak average single calcium channel current that could be elicited by a test pulse to 0 mV. The steady‐state inactivation relationship could be described by the Boltzmann equation, [1 + exp[Vm‐V0.5)/k)]‐1, with a steepness factor, k, of 7.1 mV. Nisoldipine shifted the steady‐state inactivation curve to more negative potentials by increasing the fraction of test pulses without openings. 3. The degree of nisoldipine inhibition of average single calcium channel currents increased with membrane depolarization. Depolarization of the holding potential from ‐100 to ‐55 mV decreased the concentration of nisoldipine needed for 50% inhibition (Kapp) from 12.1 to 1.9 nM in the presence of 1 microM‐Bay K 8644. 4. Membrane depolarization by external potassium (K+) of the intact artery in the presence of nisoldipine decreased contractions evoked by depolarizing test pulses. The relationship between membrane potential and contraction could be empirically described by the Boltzmann equation, with a steepness factor, k, of 7.1 mV. Increasing the nisoldipine concentration from 0.25 to 2.0 nM shifted the mid‐point of this relationship from ‐20.5 to ‐33.0 mV, without affecting the steepness factor. 5. Nisoldipine inhibition of contraction increased with membrane depolarization. Membrane depolarization from ‐68.6 to ‐30.0 mV decreased the Kapp of nisoldipine for contractions from 3.02 to 0.69 nM. Bay K 8644 (1 microM) elevated Kapp about 9.3‐fold at 5 mM‐K+. In the presence of Bay K 8644, membrane depolarization from ‐68.6 to ‐30.0 mV reduced Kapp from 28.4 to 4.0 nM. 6. In the presence of nisoldipine, the effect of membrane depolarization on the time course of development of inhibition was examined. In 3 nM‐nisoldipine, after membrane depolarization with 20 mM‐K+, the time course of development of inhibition of force could be described by a single exponential with a time constant of 16.5 min. Membrane depolarization to a more positive potential accelerated the development of inhibition. 7. The results were interpreted by a model in which nisoldipine binds with higher affinity to the inactivated state than to the resting state of calcium channels in the mesenteric artery. The approach presented here can be used to estimate the properties of steady‐state calcium channel inactivation and dihydropyridine interactions in smooth muscle cells in the intact artery under physiological conditions.(ABSTRACT TRUNCATED AT 400 WORDS)