Interaction of hydrogen sulfide with ion channels.
1. Hydrogen sulfide (H(2)S) 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 H(2)S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically. 2. H(2)S 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, H(2)S 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. H(2)S inhibited L-type Ca(2+) channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca(2+) levels. H(2)S activated small and medium conductance K(Ca) channels but its effect on BK(Ca) channels has not been consistent. 4. H(2)S-induced hyperalgesia and pro-nociception seems to be related to the sensitization of both T-type Ca(2+) channels and TRPV(1) channels. The activation of TRPV(1) and TRPA(1) by H(2)S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl(-) secretion. 5. The activation of Cl(-) channel by H(2)S has been shown as a protective mechanism for neurons from oxytosis. H(2)S 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 H(2)S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re-evaluated.
Tang
Guanghua
G
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Wu
Lingyun
L
Wang
Rui
R
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D019610:Cytoprotection; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007473:Ion Channels / Q000819:agonists / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D007473:Ion Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013440:Sulfides; D064233:Sulfonylurea Receptors; C025451:sodium bisulfide; D006862:Hydrogen Sulfide