Dataset Information

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 and Ca_V1.2 into nanocomplexes at the plasma membrane of human and mouse arterial myocytes. Hence, data reveal an AKAP5 signaling module that regulates L-type Ca²⁺ channel activity and vascular reactivity upon elevated glucose. This AKAP5-anchored nanocomplex may contribute to vascular complications during diabetic hyperglycemia.

SUBMITTER: Prada MP

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

REPOSITORIES: biostudies-literature

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AKAP5 complex facilitates purinergic modulation of vascular L-type Ca2+ channel CaV1.2.

Prada Maria Paz MP Syed Arsalan U AU Reddy Gopireddy R GR Martín-Aragón Baudel Miguel M Flores-Tamez Víctor A VA Sasse Kent C KC Ward Sean M SM Sirish Padmini P Chiamvimonvat Nipavan N Bartels Peter P Dickson Eamonn J EJ Hell Johannes W JW Scott John D JD Santana Luis F LF Xiang Yang K YK Navedo Manuel F MF Nieves-Cintrón Madeline M

Nature communications 20201020 1

The L-type Ca2+ channel CaV1.2 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. ...[more]

PMID: 33082339

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Dataset Information

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

Publications

AKAP5 complex facilitates purinergic modulation of vascular L-type Ca<sup>2+</sup> channel Ca<sub>V</sub>1.2.

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