The Inotropic Peptide βARKct Improves βAR Responsiveness in Normal and Failing Cardiomyocytes Through G _βγ -Mediated L-Type Calcium Current Disinhibition

Abstract

Our study identifies a G(βγ)-dependent signaling pathway attenuating cardiomyocyte I(Ca) on βAR as molecular target for the G(βγ)-sequestering peptide βARKct. Targeted interruption of this inhibitory signaling pathway by βARKct confers improved βAR contractile responsiveness through increased I(Ca) without enhancing regular or restoring abnormal cAMP-signaling. βARKct-mediated improvement of I(Ca) rendered cardiomyocytes neither susceptible to βAR-induced damage nor arrhythmogenic sarcoplasmic reticulum Ca²(+) leakage.