Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes

摘要: Pathological vasoconstriction compromises blood flow to tissues and contributes various conditions associated with diabetes, including stroke, hypertension, diabetic neuropathy, retinopathy. Nystoriak et al . identified a molecular signaling complex—protein kinase A, scaffolding protein in the AKAP family, L-type calcium channel CaV1.2—in arterial myocytes from mice that mediates phosphorylation of CaV1.2 enhances activity this channel, leading vasoconstriction. Exposing isolated or humans increased extracellular glucose promoted modification activity. Furthermore, human subjects had amount at Ser1928, which resulted Arteries exhibited more pronounced response pressure than did arteries control mice. Knocking S1928A mutant form blocked response. Thus, targeting regulatory complex may prevent vascular dysfunction patients.