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Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, Sweden.

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.