Figure 8.

Regulation of K_ATP channels by vasoconstrictors and vasodilators. Schematic of the plasma membrane of a vascular SMC showing, from left to right, a G_q-protein-coupled receptor (G_qPCR), associated G-proteins and PLCβ; a K_ATP channel; and a G_s-protein-coupled receptor, associated G-proteins and AC. Black lines and arrows indicate stimulation, activation or increases; red lines indicate inhibition. These channels can be activated by a fall in intracellular ATP in the environment of these channels. In addition, vasodilators that act at G_SPCRs (isoproterenol, adenosine, prostacyclin, CGRP, etc.), stimulate AC, increase the production of cAMP and activate PKA lead to activation of K_ATP channels. Similarly, NO, acting through sGC to increase production of cGMP, activating PKG which can activate K_ATP channels. These channels also can be activated by H₂S, as shown. Conversely, increases in ATP close K_ATP channels. Vasoconstrictors that act through G_qPCRs (norepinephrine, endothelin, angiotensin II, serotonin, etc.) to activate PLCβ, the production of DAG and PKC activation will lead to closure of K_IR channels. Increases in intracellular Ca²⁺ that accompany SMC stimulation by vasoconstrictors activates protein phosphatase 2B (calcineurin), which also closes K_ATP channels by dephosphorylation. See text for more information.