%0 Journal Article
%T The AKAP Cypher/Zasp contributes to ¦Â-adrenergic/PKA stimulation of cardiac CaV1.2 calcium channels
%A Can
%A Can Yuan
%A Catterall
%A Haijie
%A Haijie Yu
%A Ruth E.
%A Ruth E. Westenbroek
%A Westenbroek
%A William A.
%A William A. Catterall
%A Yu
%A Yuan
%J JGP | The Journal of General Physiology
%D 2018
%R 10.1085/jgp.201711818
%X Stimulation of the L-type Ca2+ current conducted by CaV1.2 channels in cardiac myocytes by the ¦Â-adrenergic/protein kinase A (PKA) signaling pathway requires anchoring of PKA to the CaV1.2 channel by an A-kinase anchoring protein (AKAP). However, the AKAP(s) responsible for regulation in vivo remain unknown. Here, we test the role of the AKAP Cypher/Zasp in ¦Â-adrenergic regulation of CaV1.2 channels using physiological studies of cardiac ventricular myocytes from young-adult mice lacking the long form of Cypher/Zasp (LCyphKO mice). These myocytes have increased protein levels of CaV1.2, PKA, and calcineurin. In contrast, the cell surface density of CaV1.2 channels and the basal Ca2+ current conducted by CaV1.2 channels are significantly reduced without substantial changes to kinetics or voltage dependence. ¦Â-adrenergic regulation of these L-type Ca2+ currents is also significantly reduced in myocytes from LCyphKO mice, whether calculated as a stimulation ratio or as net-stimulated Ca2+ current. At 100 nM isoproterenol, the net ¦Â-adrenergic¨CCa2+ current conducted by CaV1.2 channels was reduced to 39 ¡À 12% of wild type. However, concentration¨Cresponse curves for ¦Â-adrenergic stimulation of myocytes from LCyphKO mice have concentrations that give a half-maximal response similar to those for wild-type mice. These results identify Cypher/Zasp as an important AKAP for ¦Â-adrenergic regulation of cardiac CaV1.2 channels. Other AKAPs may work cooperatively with Cypher/Zasp to give the full magnitude of ¦Â-adrenergic regulation of CaV1.2 channels observed in vivo.
%U http://jgp.rupress.org/content/150/6/883