Modulation of calcium-activated non-selective cation channel activity by nitric oxide in rat brown adipose tissue.
1. Single-channel calcium-activated non-selective cation currents from isolated rat brown fat cells were measured using the inside-out patch configuration of the patch-clamp technique. The existence of a possible modulatory effect of nitric oxide on the putative redox-modulatory site located on the intracellular side of the non-selective cation channel was investigated. 2. The nitric oxide-releasing substances nitroglycerin, sodium nitroprusside, S-nitrosocysteine and S-nitroso-N-acetyl-D,L-penicillamine (all at 100 microM) were able to block channel activity almost completely. 3. In each case the blockade was persistent and could not be washed away. Dithiothreitol (DTT, 2 mM) was able to reverse the blockade to a large extent, whereas oxidized DTT (2 mM) was without effect. 4. It was concluded that nitric oxide can modulate non-selective cation channel activity by oxidizing sulfhydryl groups and that this effect can be reversed by reduction.
Koivisto
A
A
Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, Sweden.
Nedergaard
J
J
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000478:Alkylation; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003545:Cysteine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D003864:Depression, Chemical; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D007473:Ion Channels; D026403:S-Nitrosothiols; D013438:Sulfhydryl Compounds; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; C021315:S-nitrosocysteine; D005996:Nitroglycerin; D010396:Penicillamine; D003545:Cysteine; D002118:Calcium