β-Adrenergic control of sarcolemmal Ca <sub>V</sub> 1.2 abundance by small GTPase Rab proteins
Silvia G. del Villar, Taylor L. Voelker, Maartje Westhoff, Gopireddy R. Reddy, Heather C. Spooner, Manuel F. Navedo, Eamonn J. Dickson, Rose E. Dixon
Abstract
Significance The L-type voltage-gated Ca 2+ channel Ca V 1.2 is essential for excitation–contraction coupling in the heart. During the fight-or-flight response, Ca V 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 Ca V 1.2 channels, driven by stimulated insertion/recycling of specific Ca V 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.