Open Accessβ-Adrenergic control of sarcolemmal Ca V 1.2 abundance by small GTPase Rab proteins
Author(s) -
Silvia Villar,
Taylor L. Voelker,
Maartje Westhoff,
Gopireddy R. Reddy,
Heather C. Spooner,
Manuel F. Navedo,
Eamonn J. Dickson,
Rose E. Dixon
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2017937118
Subject(s) - excitation–contraction coupling , phosphorylation , adrenergic receptor , chemistry , gtpase , receptor , biophysics , rab , microbiology and biotechnology , biology , biochemistry , myocyte
Significance The L-type voltage-gated Ca2+ channel CaV 1.2 is essential for excitation–contraction coupling in the heart. During the fight-or-flight response, CaV 1.2 channel activity is augmented as a result of PKA-mediated phosphorylation, downstream of β-adrenergic receptor activation. We discovered that enhanced sarcolemmal abundance of CaV 1.2 channels, driven by stimulated insertion/recycling of specific CaV 1.2-containing endosomes, is essential for β-adrenergic receptor-mediated regulation of these channels in the heart. These data reveal a conceptual framework of this critical and robust pathway for on-demand tuning of cardiac excitation–contraction coupling during fight-or-flight.