Matzel L D, Rogers R F, Talk A C
Department of Psychology, Rutgers University, New Brunswick, NJ 08903, USA.
Neuroscience. 1996 Oct;74(4):1175-85. doi: 10.1016/0306-4522(96)00188-1.
Hydrolysis-resistant activation of G-proteins by extracellular perfusion of fluoride ions was examined in Type B cells isolated from the cerebral ganglion of the marine mollusc Hermissenda. Under single-electrode voltage-clamp, modulation by aluminum fluoride ions of several classes of outward K+ currents as well as an inward Ca2+ current was observed. Following injection of the Ca2+ chelator EGTA, aluminum fluoride ions selectively increased a slow, voltage-dependent K+ current (IK) within 5 min of application, while in the absence of EGTA, aluminum fluoride ions induced a small, transient reduction of IK. Neither the magnitude nor steady-state inactivation of a fast, voltage-dependent K+ current (IA), nor a slow, Ca2+-dependent K+ current (IK-Ca), were affected by aluminum fluoride ions. In contrast, when perfusion of aluminum fluoride ions was accompanied by a repetitive depolarization and a concomitant increase in intracellular Ca2+, both IA and the combined late currents (IK and IK-Ca) were markedly reduced, a reduction which was not observed following depolarization alone or if the pairing of aluminum fluoride ions and depolarization was preceded by an injection of EGTA. The reduction of membrane conductance by the pairing of aluminum fluoride ions with depolarization could not be accounted for by an increased Ca2+ conductance, as aluminum fluoride ions produced only a small decrease in the voltage-dependent Ca2+ current. In total, these results indicate that regulatory G-proteins may bidirectionally modulate neuronal K+ currents, the direction of which is dependent on intracellular Ca2+ concentration. Such a dual regulatory mechanism may contribute to the modulation of membrane excitability observed when presynaptic activity is paired with postsynaptic depolarization, and thus may contribute to some forms of activity-dependent plasticity involving metabatropic receptors.
在从海洋软体动物海兔的脑神经节分离出的B型细胞中，研究了通过细胞外灌注氟离子对G蛋白进行抗水解激活的情况。在单电极电压钳制下，观察到氟化铝离子对几类外向钾离子电流以及内向钙离子电流的调制作用。注入钙离子螯合剂乙二醇双四乙酸（EGTA）后，氟化铝离子在施加后的5分钟内选择性地增加了一种缓慢的、电压依赖性钾离子电流（IK），而在没有EGTA的情况下，氟化铝离子引起IK的小幅短暂降低。快速的、电压依赖性钾离子电流（IA）以及缓慢的、钙离子依赖性钾离子电流（IK-Ca）的幅度和稳态失活均不受氟化铝离子影响。相反，当氟化铝离子灌注伴随着重复去极化以及细胞内钙离子的相应增加时，IA以及合并的晚期电流（IK和IK-Ca）均显著降低，而单独去极化后未观察到这种降低，或者在注入EGTA后再进行氟化铝离子与去极化的配对也未观察到这种降低。氟化铝离子与去极化配对导致的膜电导降低不能用钙离子电导增加来解释，因为氟化铝离子仅使电压依赖性钙离子电流略有降低。总体而言，这些结果表明调节性G蛋白可能双向调节神经元钾离子电流，其方向取决于细胞内钙离子浓度。这种双重调节机制可能有助于解释当突触前活动与突触后去极化配对时所观察到的膜兴奋性调制，因此可能有助于某些形式的涉及代谢型受体的活动依赖性可塑性。
