AKAP5 complex facilitates purinergic modulation of vascular L-type Ca2+ channel CaV1.2
Maria Paz Prada,
Arsalan U. Syed,
Gopireddy R. Reddy,
Miguel Martín-Aragón Baudel,
Víctor A. Flores-Tamez,
Kent C. Sasse,
Sean M. Ward,
Padmini Sirish,
Nipavan Chiamvimonvat,
Peter Bartels,
Eamonn J. Dickson,
Johannes W. Hell,
John D. Scott,
Luis F. Santana,
Yang K. Xiang,
Manuel F. Navedo () and
Madeline Nieves-Cintrón ()
Additional contact information
Maria Paz Prada: University of California Davis
Arsalan U. Syed: University of California Davis
Gopireddy R. Reddy: University of California Davis
Miguel Martín-Aragón Baudel: University of California Davis
Víctor A. Flores-Tamez: University of California Davis
Kent C. Sasse: Sasse Surgical Associates
Sean M. Ward: University of Nevada Reno
Padmini Sirish: University of California Davis
Nipavan Chiamvimonvat: University of California Davis
Peter Bartels: University of California Davis
Eamonn J. Dickson: University of California Davis
Johannes W. Hell: University of California Davis
John D. Scott: University of Washington Seattle
Luis F. Santana: University of California Davis
Yang K. Xiang: University of California Davis
Manuel F. Navedo: University of California Davis
Madeline Nieves-Cintrón: University of California Davis
Nature Communications, 2020, vol. 11, issue 1, 1-14
Abstract:
Abstract 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. 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 CaV1.2 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.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18947-y
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DOI: 10.1038/s41467-020-18947-y
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