Abstract
Elevation of intracellular pH (pH i) enhances the activity of native L-type Ca 2+ channels in cardiac and smooth muscle. We studied the modulation by pH i of expressed L-type Ca 2+ channels comprised of either the α 1C subunits alone or of α 1C plus β 2a subunits. Ca 2+ 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 NH 4Cl (20 mM) or by elevation of extracellular pH to 8.5. Elevation of pH i enhanced the activity of Ca 2+ channels derived by coexpression of α 1C and β 2a subunits. This alkalosis-induced stimulation of channel activity was mainly due to an increase in channel availability. Channels derived by expression of α 1C alone were not affected by intracellular alkalosis. Our results demonstrate that the pH i sensitivity of L-type Ca 2+ channels is conferred by the β subunit of the channel complex.
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