Adrenergic Ca _V 1.2 Activation via Rad Phosphorylation Converges at α _1C I-II Loop

Abstract

Ca²⁺ channel activity is dynamically modulated under basal conditions, during β-adrenergic stimulation, and in heart failure by mechanisms converging at the α_1C I-II loop. Ca_Vβ binding to α_1C stabilizes an increased channel open probability gating mode by a mechanism that requires an intact rigid linker between the β-subunit binding site in the I-II loop and the channel pore. Release of Rad-mediated inhibition of Ca²⁺ channel activity by β-adrenergic agonists/PKA also requires this rigid linker and β-binding to α_1C.