Interaction of Hydrogen Sulfide and Adenosine Triphosphate-Sensitive Potassium Channels in Vascular Smooth Muscle Cells

Abstract

KATP channels link adenosine triphosphate (ATP) production to cellular functions by modulating membrane potentials and transmembrane ion flux. In vascular smooth muscle cells (VSMCs), opening of KATP channels in plasma membrane leads to membrane hyperpolarization and muscle relaxation. The functionality of KATP channels in mitochondrial membrane affects the redox status of cells and the outcome of ischemic damage. The modulation of KATP channels by endogenous substances and pharmacological agents has been known. The interaction of hydrogen sulfide (H2S) with KATP channels in VSMCs attracted a great deal of attention. By stimulating KATP channels, H2S lowered blood pressure of rats and relaxed vascular smooth muscles. Whole-cell patch-clamp studies revealed that H2S increased KATP channel currents and hyperpolarized membrane of single VSMCs. Because the known second-messenger systems are not apparently altered by H2S, a direct interaction of KATP channels and H2S has been assumed. Among mechanisms that underlie the effect of H2S on KATP channels are altered ATP metabolism, generation of thiyl free radicals, and sulfuration of KATP channel proteins. Unmasking the molecular mechanisms for the effect of H2S on the structure and function of KATP channels will help researchers to understand the cellular effects of H2S. This advance in knowledge will also have the potential to reveal a novel sulfuration mechanism by which many membrane proteins can be directly modified by H2S.