BIDIRECTIONAL REGULATION OF NEURONAL POTASSIUM CURRENTS BY THE G-PROTEIN ACTIVATOR ALUMINUM FLUORIDE AS A FUNCTION OF INTRACELLULAR CALCIUM-CONCENTRATION

Hydrolysis-resistant activation of G-proteins by extracellular perfusi on of fluoride ions was examined in Type B cells isolated from the cer ebral ganglion of the marine mollusc Hermissenda. Under single-electro de voltage-clamp, modulation by aluminum fluoride ions of several clas ses of outward K+ currents as well as an inward Ca2+ current was obser ved. Following injection of the Ca2+ chelator EGTA, aluminum fluoride ions selectively increased a slow, voltage-dependent K+ current (I-K) within 5 min of application, while in the absence of EGTA, aluminum fl uoride ions induced a small, transient reduction of I-K. Neither the m agnitude nor steady-state inactivation of a fast, voltage-dependent K current (I-A), nor a slow, Ca2+-dependent K+ current (I-K-Ca), were a ffected by aluminum fluoride ions. In contrast, when perfusion of alum inum fluoride ions was accompanied by a repetitive depolarization and a concomitant increase in intracellular Ca2+, both I-A and the combine d late currents (I-K and I-K-Ca) were markedly reduced. a reduction wh ich was not observed following depolarization alone or if the pairing of aluminum fluoride ions and depolarization was preceded by an inject ion of EGTA. The reduction of membrane conductance by the pairing of a luminum fluoride ions with depolarization could not be accounted for b y an increased Ca2+ conductance, as aluminum fluoride ions produced on ly a small decrease in the voltage-dependent Ca2+ current. In total, t hese results indicate that regulatory G-proteins may bidirectionally m odulate neuronal K+ currents, the direction of which is dependent on i ntracellular Ca2+ concentration. Such a dual regulatory mechanism may contribute to the modulation of membrane excitability observed when pr esynaptic activity is paired with postsynaptic depolarization, and thu s may contribute to some forms of activity-dependent plasticity involv ing metabatropic receptors. Copyright (C) 1996 IBRO. Published by Else vier Science Ltd.