Interaction of hydrogen sulfide with ion channels

P>1. Hydrogen sulfide (H2S) is a signalling gasotransmitter. It targets different ion channels and receptors, and fulfils its various roles in modulating the functions of different systems. However, the interaction of H2S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically. 2. H2S is the first identified endogenous gaseous opener of ATP-sensitive K+ channels in vascular smooth muscle cells. Through the activation of ATP-sensitive K+ channels, H2S lowers blood pressure, protects the heart from ischemia and reperfusion injury, inhibits insulin secretion in pancreatic beta cells, and exerts anti-inflammatory, anti-nociceptive and anti-apoptotic effects. 3. H2S inhibited L-type Ca2+ channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca2+ levels. H2S activated small and medium conductance K-Ca channels but its effect on BKCa channels has not been consistent. 4. H2S-induced hyperalgesia and pro-nociception seems to be related to the sensitization of both T-type Ca2+ channels and TRPV1 channels. The activation of TRPV1 and TRPA(1) by H2S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl- secretion. 5. The activation of Cl- channel by H2S has been shown as a protective mechanism for neurons from oxytosis. H2S also potentiates N-methyl-d-aspartic acid receptor-mediated currents that are involved in regulating synaptic plasticity for learning and memory. 6. Given the important modulatory effects of H2S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re-evaluated.