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

Elevation of intracellular pH (pHi) enhances the activity of native L‐type Ca2+ channels in cardiac and smooth muscle. We studied the modulation by pHi of expressed L‐type Ca2+ channels comprised of either the α1C subunits alone or of α1C plus β2a subunits. Ca2+ channels were expressed in human embryonic kidney cells (HEK 293) and pHi 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 pHi enhanced the activity of Ca2+ channels derived by coexpression of α1C and β2a subunits. This alkalosis‐induced stimulation of channel activity was mainly due to an increase in channel availability. Channels derived by expression of α1C alone were not affected by intracellular alkalosis. Our results demonstrate that the pHi sensitivity of L‐type Ca2+ channels is conferred by the β subunit of the channel complex.