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海兔中突触前易化和行为敏感化背后的钙电流调制机制。

Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia.

作者信息

Klein M, Kandel E R

出版信息

Proc Natl Acad Sci U S A. 1980 Nov;77(11):6912-6. doi: 10.1073/pnas.77.11.6912.

DOI:10.1073/pnas.77.11.6912
PMID:6256770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC350401/
Abstract

Behavioral sensitization of the gill-withdrawal reflex of Aplysia is caused by presynaptic facilitation at the synapses of the mechanoreceptor sensory neurons of the reflex onto the motor neurons and interneurons. The presynaptic facilitation has been shown to be simulated by serotonin (the putative presynaptic facilitatory transmitter) and by cyclic AMP and to be accompanied by an increase in the Ca2+ current of sensory neuron cell bodies exposed to tetraethylammonium. This increase in the Ca2+ current could result from either a direct action on the Ca2+ channel or an action on an opposing K+ current. Here we report voltage clamp experiments which indicate that the increase in Ca2+ current associated with presynaptic facilitation results from a decrease in a K+ current. Stimulation of the connective (the pathway that mediates sensitization) or application of serotonin causes a decrease in a voltage-sensitive, steady-state outward current measured under voltage clamp as well as an increase in the transient net inward and a decrease in the transient outward currents elicited by brief depolarizing command steps. The reversal potential of the steady-state synaptic current is sensitive to extracellular K+ concentration, and both the steady-state synaptic current and the changes in the transient currents are blocked by K+ current blocking agents and by washout of K+. These results suggest that serotonin and the natural transmitter released by connective stimulation act to decrease a voltage-sensitive K+ current. The decrease in K+ current prolongs the action potential, and this in turn increases the duration of the inward Ca2+ current and thereby enhances transmitter release.

摘要

海兔鳃缩反射的行为敏感化是由该反射的机械感受器感觉神经元与运动神经元及中间神经元之间突触处的突触前易化引起的。已表明,血清素(假定的突触前易化递质)和环磷酸腺苷可模拟突触前易化,且伴随暴露于四乙铵的感觉神经元胞体的Ca2+电流增加。Ca2+电流的这种增加可能是由于对Ca2+通道的直接作用,或者是对相反的K+电流的作用。在此,我们报告电压钳实验,其表明与突触前易化相关的Ca2+电流增加是由K+电流减少所致。刺激连接体(介导敏感化的通路)或应用血清素会导致在电压钳下测量的电压敏感性稳态外向电流减少,以及短暂去极化指令步骤引发的瞬时内向净电流增加和瞬时外向电流减少。稳态突触电流的反转电位对细胞外K+浓度敏感,并且稳态突触电流以及瞬时电流的变化均被K+电流阻断剂和K+洗脱所阻断。这些结果表明,血清素和连接体刺激释放的天然递质作用于减少电压敏感性K+电流。K+电流的减少延长了动作电位,进而增加了内向Ca2+电流的持续时间,从而增强了递质释放。

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