Differential modulation of N-type 1B and P/Q-type 1A calcium channels by different G protein subunit isoforms

J Physiol. 2000 Sep 1;527 Pt 2(Pt 2):203-12. doi: 10.1111/j.1469-7793.2000.00203.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, N-Type / drug effects*
  • Calcium Channels, Q-Type / drug effects*
  • Cattle
  • Cell Line
  • Electrophysiology
  • Heterotrimeric GTP-Binding Proteins / pharmacology*
  • Humans
  • Isomerism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kinetics
  • Patch-Clamp Techniques
  • Receptors, Presynaptic / drug effects
  • Synaptic Transmission / drug effects
  • Transfection


  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • Calcium Channels, Q-Type
  • Receptors, Presynaptic
  • Heterotrimeric GTP-Binding Proteins