INHIBITION OF CALCIUM INFLUX AND CALCIUM CURRENT BY GAMMA-AMINOBUTYRIC-ACID IN SINGLE SYNAPTIC TERMINALS

INHIBITION OF CALCIUM INFLUX AND CALCIUM CURRENT BY GAMMA-AMINOBUTYRIC-ACID IN SINGLE SYNAPTIC TERMINALS
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DOI:
10.1073/pnas.88.16.7135
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发表时间:
1991-08-01
影响因子:
11.1
通讯作者:
MATTHEWS, G
MATTHEWS, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HEIDELBERGER, R;MATTHEWS, G

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在离体视网膜双极神经元单个突触终末上研究了γ-氨基丁酸(GABA)对Ca内流和Ca电流的抑制作用。用荧光钙指示剂fura-2测定细胞内钙浓度([Ca]i)表明,GABA能有效地抑制高细胞外钾浓度([K]o)引起的钙内流。这种抑制归因于GABA A型(GABA(A))受体激活的氯离子电导,其阻止双极神经元充分去极化以激活Ca电流,即使响应于增加的[K]o。钙电流的膜片钳记录揭示了GABA的第二种效应:钙电流的GTP依赖性抑制。这种抑制不是由GABA(A)受体介导的,但是巴氯芬不能模拟GABA的作用,巴氯芬结合GABA B型(GABA(B))受体,并且已知其抑制其它系统中的Ca电流。这表明不同类型的GABA(B)样受体参与GABA对Ca电流的抑制。GABA没有引起钙电流的整体抑制,相反,钙通道激活的电压依赖性转移到更多的去极化电位。因此,GABA对Ca电流的最大抑制发生在生理电位范围内。
Inhibition of Ca influx and Ca current by gamma-aminobutyric acid (GABA) was studied in single synaptic terminals of isolated retinal bipolar neurons. Measurements of intracellular Ca concentration ([Ca]i) using the fluorescent Ca indicator fura-2 showed that GABA potently inhibited Ca influx into the terminal elicited by high extracellular K concentration ([K]o). This inhibition was attributed to GABA type A (GABA(A)) receptor-activated chloride ion conductance that prevented bipolar neurons from depolarizing sufficiently to activate the Ca current, even in response to increased [K]o. Patch-clamp recordings of the Ca current revealed a second effect of GABA: GTP-dependent inhibition of the Ca current. This inhibition was not mediated by GABA(A) receptors, but baclofen, which binds to the GABA type B (GABA(B)) receptor and is known to inhibit the Ca current in other systems, was not able to mimic the action of GABA. This suggests the involvement of a different type of GABA(B)-like receptor in the inhibition of Ca current by GABA. GABA did not cause an overall suppression of the Ca current; rather, the voltage-dependence of Ca-channel activation was shifted to more depolarized potentials. Thus, maximal inhibition of the Ca current by GABA occurred in the physiological range of potential.