Reconstitution of β-adrenergic regulation of CaV1.2: Rad-dependent and Rad-independent protein kinase A mechanisms.
作者： Nathan Dascal , Orna Chomsky-Hecht , Veit Flockerzi , Enno Klussmann , Vladimir Tsemakhovich
关键词:
摘要: L-type voltage-gated CaV1.2 channels crucially regulate cardiac muscle contraction. Activation of β-adrenergic receptors (β-AR) augments contraction via protein kinase A (PKA)-induced increase calcium influx through channels. To date, the full β-AR cascade has never been heterologously reconstituted. recent study identified Rad, a inhibitory protein, as essential for PKA regulation CaV1.2. We corroborated this finding and reconstituted complete pathway with agonist activation β1-AR or β2-AR in Xenopus oocytes. found, distinguished between, two distinct pathways modulation CaV1.2: Rad dependent (∼80% total) independent. The system reproduces known features cardiomyocytes reveals several aspects: differential posttranslationally modified variants versus activity. This allows addressing central unresolved issues β-AR-CaV1.2 will facilitate development therapies catecholamine-induced pathologies.
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