Co-expression of the beta-subunit with the alpha 1-subunit resulted in a >35-fold increase in (+)-isradipine binding affinity (Ki = 0.9 nM vs 34.3 nM) due to decreased dissociation.
Effect estimate: > 35-fold increase
Absolute Event Rate: 0.9% vs 34.3%
A Ca2+ channel alpha 1-subunit derived from rabbit heart was transiently expressed in COS-7 cells. The dihydropyridine (+)-isradipine had low affinity (Ki = 34.3 nM) for the alpha 1-subunit in the absence of the beta-subunit due to rapid dissociation (k-1 = 0.11 min-1). Co-expression of the beta-subunit resulted in a > 35-fold increase in (+)-isradipine binding affinity (Ki = 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 Ca2+ ions for the channel. Our data suggest that the beta-subunit affects the coordination of Ca2+ ions with sites that are coupled to the dihydropyridine binding domain and by this mechanism increases the affinity for these ligands.
Mitterdorfer et al. (Mon,) reported a other. Co-expression of the beta-subunit vs. Absence of the beta-subunit (alpha 1-subunit alone) was evaluated on (+)-isradipine binding affinity (Ki) (> 35-fold increase). Co-expression of the beta-subunit with the alpha 1-subunit resulted in a >35-fold increase in (+)-isradipine binding affinity (Ki = 0.9 nM vs 34.3 nM) due to decreased dissociation.
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