Injection of a peptide displacing PP2A from endogenous Cav1.2 increased basal and isoproterenol-stimulated L-type Ca2+ currents in acutely isolated cardiomyocytes.
Anchoring of PP2A at residues 1965-1971 of the Ca(v)1.2 C-terminus negatively regulates cardiac L-type currents by counterbalancing basal and stimulated phosphorylation.
The L-type Ca(2+) channel Ca(v)1.2 forms macromolecular signaling complexes that comprise the β(2) adrenergic receptor, trimeric G(s) protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA) for efficient signaling in heart and brain. The protein phosphatases PP2A and PP2B are part of this complex. PP2A counteracts increase in Ca(v)1.2 channel activity by PKA and other protein kinases, whereas PP2B can either augment or decrease Ca(v)1.2 currents in cardiomyocytes depending on the precise experimental conditions. We found that PP2A binds to two regions in the C-terminus of the central, pore-forming α(1) subunit of Ca(v)1.2: one region spans residues 1795-1818 and the other residues 1965-1971. PP2B binds immediately downstream of residue 1971. Injection of a peptide that contained residues 1965-1971 and displaced PP2A but not PP2B from endogenous Ca(v)1.2 increased basal and isoproterenol-stimulated L-type Ca(2+) currents in acutely isolated cardiomyocytes. Together with our biochemical data, these physiological results indicate that anchoring of PP2A at this site of Ca(v)1.2 in the heart negatively regulates cardiac L-type currents, likely by counterbalancing basal and stimulated phosphorylation that is mediated by PKA and possibly other kinases.
Xu et al. (Fri,) reported a other. Peptide containing residues 1965-1971 was evaluated on Basal and isoproterenol-stimulated L-type Ca(2+) currents. Injection of a peptide displacing PP2A from endogenous Cav1.2 increased basal and isoproterenol-stimulated L-type Ca2+ currents in acutely isolated cardiomyocytes.
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