Expression of the alpha(2)delta subunit interferes with prepulse facilitation in cardiac L-type calcium channels

Biophys J. 2000 Jun;78(6):2959-72. doi: 10.1016/S0006-3495(00)76835-4.

Abstract

We investigated the role of the accessory alpha(2)delta subunit on the voltage-dependent facilitation of cardiac L-type Ca(2+) channels (alpha(1C)). alpha(1C) Channels were coexpressed in Xenopus oocytes with beta(3) and alpha(2)delta calcium channel subunits. In alpha(1C) + beta(3), the amplitude of the ionic current (measured during pulses to 10 mV) was in average approximately 1.9-fold larger after the application of a 200-ms prepulse to +80 mV. This phenomenon, commonly referred to as voltage-dependent facilitation, was not observed when alpha(2)delta was coexpressed with alpha(1C) + beta(3). In alpha(1C) + beta(3), the prepulse produced a left shift ( approximately 40 mV) of the activation curve. Instead, the activation curve for alpha(1C) + beta(3) + alpha(2)delta was minimally affected by the prepulse and had a voltage dependence very similar to the G-V curve of the alpha(1C) + beta(3) channel facilitated by the prepulse. Coexpression of alpha(2)delta with alpha(1C) + beta(3) seems to mimic the prepulse effect by shifting the activation curve toward more negative potentials, leaving little room for facilitation. The facilitation of alpha(1C) + beta(3) was associated with an increase of the charge movement. In the presence of alpha(2)delta, the charge remained unaffected after the prepulse. Coexpression of alpha(2)delta seems to set all the channels in a conformational state from where the open state can be easily reached, even without prepulse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels, L-Type / chemistry*
  • Calcium Channels, L-Type / physiology*
  • Cell Membrane / physiology
  • Electric Stimulation
  • Female
  • Heart / physiology*
  • Macromolecular Substances
  • Membrane Potentials
  • Oocytes / physiology
  • Patch-Clamp Techniques
  • Rabbits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Time Factors
  • Xenopus laevis

Substances

  • Calcium Channels, L-Type
  • Macromolecular Substances
  • Recombinant Proteins