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 w ere measured in transiently transfected HEK293 cells. 2. beta(1A) subu nit coexpression increased the maximal whole-cell conductance (G(max)) measured in 10 mM Ba2+ from 91 +/- 11 to 833 +/- 107 pS pF(-1) withou t 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 eleve n cells exhibited gating currents above the limits of detection, where as eight out of eight beta(1A) coexpressing cells had measurable gatin g currents). The gating currents were integrated to measure the intram embrane 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 t o 243 +/- 30 pS fC(-1) with beta(1A) coexpression, demonstrating that the beta(1A) subunit changes the gating of alpha(1C) channels to favou r 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) subun it coexpression increases the number of functional surface membrane ch annels.