Differential modulation of N-type 1B and P/Q-type 1A calcium channels by different G protein subunit isoforms.
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 Gbeta subtype co-expressed. Both the absolute and relative magnitudes of Gbeta 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 Gbeta 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 Gbeta 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 Gbeta subtypes mediated different degrees of slowing of activation kinetics. The differential modulation of P/Q- and N-type channels by various Gbeta subtypes may provide a mechanism for fine tuning the amount of calcium entering the presynaptic nerve termini.
Arnot
M I
MI
Neuroscience and Smooth Muscle Research Groups, Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Canada.
Stotz
S C
SC
Jarvis
S E
SE
Zamponi
G W
GW
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D020907:Calcium Channels, Q-Type / Q000187:drug effects*; D002417:Cattle; D002460:Cell Line; D004594:Electrophysiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000494:pharmacology*; D006801:Humans; D007536:Isomerism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D018408:Patch-Clamp Techniques; D017661:Receptors, Presynaptic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D014162:Transfection
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020907:Calcium Channels, Q-Type; D017661:Receptors, Presynaptic; D020962:Heterotrimeric GTP-Binding Proteins