COMPARISON OF N-TYPE AND P Q-TYPE VOLTAGE-GATED CALCIUM-CHANNEL CURRENT INHIBITION/

Activation of N- and P/Q-type voltage-gated calcium channels triggers neurotransmitter release at central and peripheral synapses, These cha nnels are targets for regulatory mechanisms, including inhibition by G -protein-linked receptors. Inhibition of P/Q-type channels has been le ss well studied than the extensively characterized inhibition of N-typ e channels, but it is thought that they are inhibited by similar mecha nisms although possibly to a lesser extent than N-type channels. The a im of this study was to compare the inhibition of the two channel type s. Calcium currents were recorded from adrenal chromaffin cells and is olated by the selective blockers omega-conotoxin GVIA (1 mu M) and ome ga-agatoxin IVA (400 nM), The inhibition was elicited by ATP (100 mu M ) OF intracellular application of GTP-gamma-S. It was classified as vo ltage-sensitive (relieved by a conditioning prepulse) or voltage-insen sitive (present after a conditioning prepulse). The voltage-insensitiv e inhibition accounted for a 20% reduction of both currents, whereas t he voltage-sensitive inhibition reduced the N-type current by 45% but the P/Q-type current by 18%. However, the voltage dependence of the in hibition, the time course of relief from inhibition during a condition ing prepulse, and the time course of reinhibition after such a prepuls e showed few differences between the N- and P/Q-type channels, Assumin g a simple bimolecular reaction, our data suggest that changes in the kinetics of the G-protein/channel interaction alone cannot explain the differences in the inhibition of the N- and P/Q-type calcium channels , The subtle differences in inhibition may facilitate the selective re gulation of neurotransmitter release.