Acid sensing ionic channels: modulation by redox reagents.
Acid-sensing ion channels (ASICs) are widely expressed in mammalian sensory neurons and supposedly play a role in nociception and acid sensing. In the course of functioning the redox status of the tissue is subjected to changes. Using whole-cell patch-clamp/concentration clamp techniques we have investigated the effect of redox reagents on the ASIC-like currents in the sensory ganglia and hippocampal neurons of rat. The reducing agent dithiothreitol (DTT), when applied in the concentrations 1-2 mM, reversibly potentiates proton-activated currents, while the oxidizing reagent 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) causes their inhibition. The EC50 and Hill coefficient for the activation of ASIC-like currents by protons are not affected by DTT. Redox modulation of proton-activated currents is independent on the membrane potential and on the level of pH used for the current activation. The endogenous antioxidant tripeptide glutathione (its reduced form, g-l-glutamyl-l-cysteinyl-glycine, GSH) also potentiates proton-activated currents. Our results indicate that ASIC-like currents are susceptible to regulation by redox agents.
Andrey
Fedorenko
F
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Tsintsadze
Timur
T
Volkova
Tatyana
T
Lozovaya
Natalia
N
Krishtal
Oleg
O
D062565:Acid Sensing Ion Channels; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*
D062565:Acid Sensing Ion Channels; D007202:Indicators and Reagents; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D004228:Dithionitrobenzoic Acid; D012964:Sodium; D005978:Glutathione; D002118:Calcium