Enhancement of ionic current and charge movement by coexpression of calcium channel β1A subunit with α1C subunit in a human embryonic kidney cell line

1. Coexpression of the β subunit with the α_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. β_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 α_1C subunit (only four out of eleven cells exhibited gating currents above the limits of detection, whereas eight out of eight β_1A coexpressing cells had measurable gating currents). The gating currents were integrated to measure the intramembrane charge 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 β_1A coexpression, demonstrating that the β_1A subunit changes the gating of α_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 β_1A subunit coexpression. The major effect is due to a 3·7-fold increase in Q_on,max, demonstrating that β_1A subunit coexpression increases the number of functional surface membrane channels.