Essential role of the beta subunit in modulation of C-class L-type Ca2+ channels by intracellular pH

Elevation of intracellular pH (pH(i)) enhances the activity of native L-type Ca2+ channels in cardiac and smooth muscle. We studied the modulation by pH(i) of expressed L-type Ca2+ channels comprised of either the alpha(1C) subunits alone or of alpha(1C) plus beta(2a) subunits. Ca2+ channels were expressed in human embryonic kidney cells (HEK 293) and pH(i) was increased from a basal level of 7.3 to 8.3 by exposure of cells to NH4Cl (20 mM) or by elevation of extracellular pH to 8.5. Elevation of pH(i) enhanced the activity of Ca2+ channels derived by coexpression of alpha(1C) and beta(2a) subunits. This alkalosis-induced stimulation of channel activity was mainly due to an increase in channel availability. Channels derived by expression of alpha(1C) alone were not affected by intracellular alkalosis. Our results demonstrate that the pH(i) sensitivity of L-type Ca2+ channels is conferred by the beta subunit of the channel complex. (C) 1997 Federation of European Biochemical Societies.