Differential modulation of N-type alpha1B and P/Q-type alpha1A calcium channels by different G protein beta subunit isoforms

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Differential modulation of N-type $alpha$ _1B and P/Q-type $alpha$ _1A calcium channels by different G protein $beta$ subunit isoforms

Michelle I. Arnot, Stephanie C. Stotz, Scott E. Jarvis and Gerald W. Zamponi

Neuroscience and Smooth Muscle Research Groups, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Canada

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 $beta$ subunits via strong depolarizing voltage prepulses.
For N- and P/Q-type channels, the magnitude of inhibition was dependent on the G subtype co-expressed.
Both the absolute and relative magnitudes of G subunit-induced inhibition of P/Q-type channels differed from those observed with the N-type channel.
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 G subunits by varying either the duration between the pre- and the test pulse or the length of the prepulse.
For each channel subtype, we observed a differential G subunit rank order with regard to the rates of re-inhibition and recovery from inhibition.
On average, P/Q-type channels exhibited more rapid rates of recovery from inhibition than those observed with N-type channels.
Different G subtypes mediated different degrees of slowing of activation kinetics.
The differential modulation of P/Q- and N-type channels by various G subtypes may provide a mechanism for fine tuning the amount of calcium entering the presynaptic nerve termini.

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