Elevated Ca2+ sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells

摘要: Ca+ sparklets are subcellular Ca2+ signals produced by the opening of L-type channels (LTCCs). In cerebral arterial myocytes, sparklet activity varies regionally, resulting in low and high activity, “persistent” sites. Although increased influx via LTCCs myocytes has been implicated chain events contributing to vascular dysfunction during acute hyperglycemia diabetes, mechanisms underlying these pathological changes remain unclear. Here, we tested hypothesis that contributes higher artery smooth muscle an animal model non-insulin-dependent, type 2 diabetes: dB/dB mouse. Consistent with this hypothesis, elevation extracellular glucose from 10 20 mM density persistent sites as well amplitude LTCC currents wild-type myocytes. Furthermore, were than control We found activation PKA contributed diabetes. addition, interaction between scaffolding protein A-kinase anchoring was critical for after hyperglycemia. Accordingly, inhibition equalized cells. These findings suggest increases increasing a PKA-dependent pathway