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急性分离的大鼠和青蛙感觉神经元胞体中二氢吡啶和ω-芋螺毒素敏感钙电流的分布:青蛙中L通道表达与直径的关系

Distribution of dihydropyridine and omega-conotoxin-sensitive calcium currents in acutely isolated rat and frog sensory neuron somata: diameter-dependent L channel expression in frog.

作者信息

Scroggs R S, Fox A P

机构信息

University of Chicago, Department of Pharmacological and Physiological Sciences, Illinois 60637.

出版信息

J Neurosci. 1991 May;11(5):1334-46. doi: 10.1523/JNEUROSCI.11-05-01334.1991.

Abstract

Calcium channel subtypes in adult rat and frog sensory neuron somata, acutely isolated from dorsal root ganglia (DRG neurons), were studied using Bay K 8644, nimodipine, and omega-conotoxin GVIA (omega-CgTx) as specific probes. The DRG neurons varied in diameter 15-60 microns (rat) and 20-80 microns (frog). Bay K 8644 produced a large increase in calcium currents of small-diameter rat DRG neurons and shifted channel activation and the peak of the I-V curve in the hyperpolarizing direction. At a physiological holding potential (HP) of -60 mV, nimodipine blocked 50% of the peak calcium current in small-diameter frog and rat DRG neurons, indicating a large L channel component. At HP -80 mV, nimodipine blocked a lower percentage of peak current in small-diameter rat and frog DRG neurons than expected (based on experiments at HP -60 mV) probably due to nimodipine's voltage dependence. At HP -60 mV, omega-CgTx blocked 25% and 50% of peak current in small-diameter rat and frog DRG neurons, respectively. Omega-CgTx blocked a larger percentage of current at HP -80 mV than at -60 mV, probably because of the repriming of N channels. Observation of nimodipine- and Bay K 8644-sensitive calcium current in small-diameter rat and frog DRG neurons after omega-CgTx treatment, suggests that omega-CgTx is not a potent L channel blocker. The combination of omega-CgTx and nimodipine blocked all current in small-diameter frog DRG neurons but left a small portion of current unblocked in small-diameter rat DRG neurons at HP -60 mV, suggesting the possibility of omega-CgTx- and nimodipine-insensitive calcium channels in rat DRG neurons. Calcium current in most large-diameter frog DRG neurons was insensitive to nimodipine, but was completely blocked by omega-CgTx. This indicates significant variation in the expression of calcium channel subtypes in small- and large-diameter frog DRG neurons, which may subserve different sensory modalities.

摘要

使用Bay K 8644、尼莫地平以及ω-芋螺毒素GVIA(ω-CgTx)作为特异性探针,对从背根神经节急性分离出的成年大鼠和青蛙感觉神经元胞体中的钙通道亚型进行了研究。大鼠背根神经节神经元(DRG神经元)的直径在15 - 60微米之间,青蛙的则在20 - 80微米之间。Bay K 8644使小直径大鼠DRG神经元的钙电流大幅增加,并使通道激活以及I-V曲线的峰值向超极化方向移动。在生理钳制电位(HP)为 -60 mV时,尼莫地平阻断了小直径青蛙和大鼠DRG神经元中50%的峰值钙电流,表明存在大量的L型通道成分。在HP为 -80 mV时,尼莫地平阻断小直径大鼠和青蛙DRG神经元峰值电流的百分比低于预期(基于HP为 -60 mV时的实验结果),这可能是由于尼莫地平的电压依赖性。在HP为 -60 mV时,ω-CgTx分别阻断了小直径大鼠和青蛙DRG神经元中25%和50%的峰值电流。与 -60 mV相比,ω-CgTx在HP为 -80 mV时阻断的电流百分比更大,这可能是由于N型通道的再激活。在ω-CgTx处理后,在小直径大鼠和青蛙DRG神经元中观察到对尼莫地平和Bay K 8644敏感的钙电流,这表明ω-CgTx不是一种有效的L型通道阻滞剂。在HP为 -60 mV时,ω-CgTx和尼莫地平的组合阻断了小直径青蛙DRG神经元中的所有电流,但在小直径大鼠DRG神经元中仍有一小部分电流未被阻断,这表明大鼠DRG神经元中可能存在对ω-CgTx和尼莫地平不敏感的钙通道。大多数大直径青蛙DRG神经元中的钙电流对尼莫地平不敏感,但被ω-CgTx完全阻断。这表明小直径和大直径青蛙DRG神经元中钙通道亚型的表达存在显著差异,这可能服务于不同的感觉模式。

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