l-735821 and methoctramine

The effect of the cholinomimetic agent, bethanechol on macroscopic membrane currents was studied in dispersed cat atrial myocytes, using the whole-cell patch-clamp technique. Bethanechol activated an inward rectifying potassium current similar to I(K(ACh)), and a delayed rectifying-like outward current, similar to I(KM3) activated by pilocarpine, choline, and tetramethylammonium, and I(KM4) activated by 4-aminopyridine. The relatively specific muscarinic receptors subtype antagonists methoctramine (M(2)), and tropicamide (M(4)) inhibited both current components induced by bethanechol, suggesting a lack of specificity of these antagonists on cat atrial myocytes. The specific antagonist of M(3) receptors, para-fluoro-hexahydro-siladifenidol did not significantly inhibit the bethanechol-induced currents. In addition, pretreatment with PTX prevented activation of the bethanechol-induced inward and outward currents, suggesting that M(3) receptors are probably not involved in the bethanechol action. The I(K(ACh)) specific blocker tertiapin inhibited both inward rectifying- and delayed rectifying-like currents. These results suggest that both current components result from activation of a single channel type, likely I(K(ACh)).

Topics: Animals; Barium; Bee Venoms; Benzodiazepines; Bethanechol; Cats; Cholinergic Agents; Diamines; Heart Atria; In Vitro Techniques; Membrane Potentials; Muscarinic Agonists; Muscarinic Antagonists; Muscle Cells; Phenethylamines; Piperidines; Potassium Channel Blockers; Potassium Channels, Inwardly Rectifying; Receptor, Muscarinic M1; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Sulfonamides; Tropicamide