Calcium channels: The β‐subunit increases the affinity of dihydropyridine and Ca2+ binding sites of the α1‐subunit

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Abstract
A Ca 2+ channel α 1 -subunit derived from rabbit heart was transiently expressed in COS-7 cells. The dihydropyridine (+)-isradipine had low affinity ( K i = 34.3 nM) for the α 1 -subunit in the absence of the β-subunit due to rapid dissociation ( k −1 = 0.11 min −1 ). Co-expression of the β-subunit resulted in a ⪢ 35-fold increase in (+)-isradipine binding affinity ( K i = 0.9 nM) due to decreased dissociation ( k −1 of 0.007 min −1 ). Higher DHP binding affinity was associated with an increase of the apparent affinity of Ca 2+ ions for the channel. Our data suggest that the β-subunit affects the coordination of Ca 2+ ions with sites that are coupled to the dihydropyridine binding domain and by this mechanism increases the affinity for these ligands.