Current modulation and membrane targeting of the calcium channel α1C subunit are independent functions of the β subunit

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Abstract
The β subunits of voltage-sensitive calcium channels facilitate the incorporation of channels into the plasma membrane and modulate calcium currents. In order to determine whether these two effects of the β subunit are interdependent or independent of each other we studied plasma membrane incorporation of the channel subunits with green fluorescent protein and immunofluorescence labelling, and current modulation with whole-cell and single-channel patch-clamp recordings in transiently transfected human embryonic kidney tsA201 cells. Coexpression of rabbit cardiac muscle α1C with rabbit skeletal muscle β1a, rabbit heart/brain β2a or rat brain β3 subunits resulted in the colocalization of α1C with β and in a marked translocation of the channel complexes into the plasma membrane. In parallel, the whole-cell current density and single-channel open probability were increased. Furthermore, the β2a isoform specifically altered the voltage dependence of current activation and the inactivation kinetics. A single amino acid substitution in the β subunit interaction domain of α1C (α1CY467S) disrupted the colocalization and plasma membrane targeting of both subunits without affecting the β subunit-induced modulation of whole-cell currents and single-channel properties. These results show that the modulation of calcium currents by β subunits can be explained by β subunit-induced changes of single-channel properties, but the formation of stable α1C-β complexes and their increased incorporation into the plasma membrane appear not to be necessary for functional modulation.