AKAP5 complex facilitates purinergic modulation of vascular L-type Ca²⁺ channel Ca_V1.2.

ABSTRACT: The L-type Ca²⁺ channel Ca_V1.2 is essential for arterial myocyte excitability, gene expression and contraction. Elevations in extracellular glucose (hyperglycemia) potentiate vascular L-type Ca²⁺ channel via PKA, but the underlying mechanisms are unclear. Here, we find that cAMP synthesis in response to elevated glucose and the selective P2Y₁₁ agonist NF546 is blocked by disruption of A-kinase anchoring protein 5 (AKAP5) function in arterial myocytes. Glucose and NF546-induced potentiation of L-type Ca²⁺ channels, vasoconstriction and decreased blood flow are prevented in AKAP5 null arterial myocytes/arteries. These responses are nucleated via the AKAP5-dependent clustering of P2Y₁₁/ P2Y₁₁-like receptors, AC5, PKA

SUBMITTER: Prada MP 

PROVIDER: S-EPMC7575592 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature