Tedisamil inhibits the delayed rectifier K+ current in single smooth muscle cells of the guinea-pig portal vein.

Tedisamil is a new bradycardic agent with an inhibitory action on K+ channels in cardiac muscle, and secondary beneficial effects in experimentally induced cardiac ischemia. In whole-cell clamp studies in enzymatically dispersed, single smooth muscle cells from the guinea-pig portal vein, tedisamil inhibited the delayed rectifier K+ current (determined as the charge transferred through the cell membrane), the mean concentration for half-maximal inhibition being 2.9 microM. In contrast to controls in the absence of drugs or in the presence of the classical K+ channel blockers barium, tetraethylammonium or 4-aminopyridine, the time course of the delayed rectifier K+ current in the presence of tedisamil could no longer be fitted by a single exponential, and signs of an accelerated inactivation by tedisamil were obtained. The slow onset of the response to tedisamil applied to the outside of the vascular myocytes, and the finding that tedisamil applied directly to the cytosol via the pipette was highly effective, suggest an intracellular site of action.