Enhancement of ionic current and charge movement by coexpression of calcium channel beta(1A) subunit with alpha(1C) subunit in a human embryonic kidney cell line

1. Coexpression of the beta subunit with the alpha(1C) subunit of the cardiac L-type Ca2+ channel has been shown to increase ionic current. To examine the mechanism of this increase, ionic and gating currents were measured in transiently transfected HEK293 cells. 2. beta(1A) subunit coexpression increased the maximal whole-cell conductance (G(max)) measured in 10 mM Ba2+ from 91 +/- 11 to 833 +/- 107 pS pF(-1) without a change in the voltage dependence of activation (V-1/2: -6.1 +/- 1.1 and -6.6 +/- 0.9 mV, respectively). 3. Gating currents were smaller in cells expressing only the alpha(1C) subunit (only four out of eleven cells exhibited gating currents above the limits of detection, whereas eight out of eight beta(1A) coexpressing cells had measurable gating currents). The gating currents were integrated to measure the intramembrane char ge movement (Q). The ON charge movement (Q(on)) could be described by a Boltzmann distribution reaching a maximal value of Q(on,max). 4. The mean ratio of G(max):Q(on,max) increased from 99 +/- 6 to 243 +/- 30 pS fC(-1) with beta(1A) coexpression, demonstrating that the beta(1A) subunit changes the gating of alpha(1C) channels to favour the opening of the channels. However, this 2.5-fold change in the G(max):Q(on,max) ratio explains less than half of the 9.2-fold increase in G(max) with beta(1A) subunit coexpression. The major effect is due to a 3.7-fold increase in Q(on,max), demonstrating that beta(1A) subunit coexpression increases the number of functional surface membrane channels.