ELEMENTARY EVENTS UNDERLYING VOLTAGE-DEPENDENT G-PROTEIN INHIBITION OF N-TYPE CALCIUM CHANNELS

Voltage-dependent G-protein inhibition of N-type calcium channels redu ces presynaptic calcium entry, sharply attenuating neurotransmitter re lease, Studies in neurons demonstrate that G-proteins have multiple mo dulatory effects on N-type channels, The observed changes may reflect genuine complexity in G-protein action and/or the intricate interactio ns of multiple channels and receptors in neurons. Expression of recomb inant M2-muscarinic receptors and N-type channels in HEK 293 cells all owed voltage-dependent inhibition to be studied in isolation. In this system, receptor-activated G-proteins had only one effect: a 10-fold i ncrease in the time required for channels to first open following memb rane depolarization. There were no changes in gating after the channel first opened, and unitary currents were not detectably altered by mod ulation. Despite its simplicity, this single change successfully accou nts for the complex alterations in whole-cell current observed during G-protein inhibition in neurons.