Adrenergic Ca_V1.2 Activation via Rad Phosphorylation Converges at α_1C I-II Loop.

ABSTRACT:

Rationale

Changing activity of cardiac Ca_V1.2 channels under basal conditions, during sympathetic activation, and in heart failure is a major determinant of cardiac physiology and pathophysiology. Although cardiac Ca_V1.2 channels are prominently upregulated via activation of PKA (protein kinase A), essential molecular details remained stubbornly enigmatic.

Objective

The primary goal of this study was to determine how various factors converging at the Ca_V1.2 I-II loop interact to regulate channel activity under basal conditions, during β-adrenergic stimulation, and in heart failure.

Methods and results

We generated transgenic mice with expression of Ca_V1.2 α_1C subunits with (1) mutations ablating interaction betwee

SUBMITTER: Papa A 

PROVIDER: S-EPMC7790865 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature