Figure 1.

Proposed model for regulation of vascular contractility by P2Y₁₁-dependent regulation of L-type Ca²⁺ channels during hyperglycemia and diabetes. During hyperglycemic conditions, glucose is transported into the cells via a glucose transporter (GLUT). Inside the cell, glucose is metabolized resulting in the production of nucleotides (NUC), such as ATP and UTP. These NUC are released to the extracellular space where they activate purinergic receptors coupled to G_s proteins (i.e., P2Y₁₁). Activation of P2Y₁₁ promotes AC5 activity and localized cAMP production. This cAMP microdomain can enable a pool of PKA that is intimately associated with L-type Ca²⁺ channels to increase Ca_V1.2 phosphorylation at S1928, which will potentiate channel activity. Hyperactive L-type Ca²⁺ channels result in increased global [Ca²⁺]_i and contraction of vascular smooth muscle. Dotted line is to reflect potential close association between proteins. This figure was created using Servier Medical Art templates, which are licensed under a Creative Commons Attribution 3.0 Unported License; https://smart.servier.com.