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大鼠海马神经元原代培养物中高阈值和低阈值钙通道的动力学及药理学特性

Kinetic and pharmacological properties of high- and low-threshold calcium channels in primary cultures of rat hippocampal neurons.

作者信息

Toselli M, Taglietti V

机构信息

Istituto di Fisiologia Generale, Università di Pavia, Italy.

出版信息

Pflugers Arch. 1992 May;421(1):59-66. doi: 10.1007/BF00374734.

Abstract

The kinetic, permeability and pharmacological properties of Ca currents were investigated in primary cultures of rat hippocampal neurons. The low-voltage-activated (LVA) Ca current turned on positive to -60 mV and fully inactivated in a voltage-dependent way. This current was depressed by nickel (Ni, 40 microM) and amiloride (500 microM) and was insensitive to omega-conotoxin (omega-CgTx) (4 microM) and to the Ca agonist Bay K 8644 (5 microM). The high-voltage-activated (HVA) Ca current turned on positive to -40 mV and inactivated slowly and incompletely. This current was much less sensitive than the LVA current to Ni and amiloride but more sensitive to cadmium. omega-CgTx blocked only partially this current (about 50%) in an irreversible way. Bay K 8644 had a clear agonistic action almost exclusively on the omega-CgTx-resistant HVA current component. The present results suggest that the HVA channels, quite homogeneous for their kinetic properties and sensitivity to holding potentials, can be pharmacologically separated in two classes: (i) omega-CgTx-sensitive and Bay-K-8644-insensitive (omega-S/BK-I) and (ii) omega-CgTx-insensitive and Bay-K-8644-sensitive (omega-I/BK-S), the latter displaying a stronger Ca-dependent inactivation.

摘要

在大鼠海马神经元原代培养物中研究了钙电流的动力学、通透性和药理学特性。低电压激活(LVA)钙电流在电压为 -60 mV 时开启,并以电压依赖性方式完全失活。该电流受到镍(Ni,40 μM)和氨氯地平(500 μM)的抑制,对 ω-芋螺毒素(ω-CgTx)(4 μM)和钙激动剂 Bay K 8644(5 μM)不敏感。高电压激活(HVA)钙电流在电压为 -40 mV 时开启,失活缓慢且不完全。该电流对 Ni 和氨氯地平的敏感性远低于 LVA 电流,但对镉更敏感。ω-CgTx 仅以不可逆方式部分阻断该电流(约 50%)。Bay K 8644 几乎仅对 ω-CgTx 耐药的 HVA 电流成分具有明显的激动作用。目前的结果表明,HVA 通道在其动力学特性和对钳制电位的敏感性方面相当均匀,在药理学上可分为两类:(i)ω-CgTx 敏感且 Bay-K-8644 不敏感(ω-S/BK-I)和(ii)ω-CgTx 不敏感且 Bay-K-8644 敏感(ω-I/BK-S),后者表现出更强的钙依赖性失活。

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