Differential modulation of N-type α(1B) and P/Q-type α1Acalcium channels by different G protein β subunit isoforms

Abstract

1. Using transient calcium phosphate transfection into the human embryonic kidney tsa-201 cell line and subsequent whole-cell patch-clamp protocols, we examined the tonic modulation of cloned N- and P/Q-type calcium channels by five different G protein β subunits via strong depolarizing voltage prepulses. 2. For N- and P/Q-type channels, the magnitude of inhibition was dependent on the Gβ subtype co-expressed. 3. Both the absolute and relative magnitudes of Gβ subunit-induced inhibition of P/Q-type channels differed from those observed with the N-type channel. 4. For each calcium channel subtype, kinetics of both the prepulse-mediated recovery from inhibition and the re-inhibition following the prepulse were examined for each of the Gβ subunits by varying either the duration between the pre- and the test pulse or the length of the prepulse. 5. For each channel subtype, we observed a differential Gβ subunit rank order with regard to the rates of re-inhibition and recovery from inhibition. 6. On average, P/Q-type channels exhibited more rapid rates of recovery from inhibition than those observed with N-type channels. 7. Different Gβ subtypes mediated different degrees of slowing of activation kinetics. 8. The differential modulation of P/Q- and N-type channels by various Gβ subtypes may provide a mechanism for fine tuning the amount of calcium entering the presynaptic nerve termini.