Figure 7.

Regulation of K_IR 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_IR 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. Hyperpolarization induced by the activation of other K⁺ channels, or the closure of channels conducting Na⁺, Ca²⁺, or Cl₋ and/or increases in extracellular K⁺ concentration are the major stimuli for activation of vascular SMC K_IR 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_IR channels. Similarly, NO, acting through sGC to increase production of cGMP, activated protein kinase G which can activate K_IR channels. Conversely, membrane depolarization due to closure of other K⁺ channels or opening of channels that conduct Na⁺, Ca²⁺, or Cl₋ will close K_IR channels. Vasoconstrictors that act through G_qPCRs (norepinephrine, endothelin, angiotensin II, 5-HT, etc.) to activate PLCβ, the production of DAG and PKC activation lead to closure of K_IR channels. See text for more information.