The cholinomimetic agent bethanechol activates IK(ACh) in feline atrial myocytes
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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 IK(ACh), and a delayed rectifying-like outward current, similar to IKM3 activated by pilocarpine, choline, and tetramethylammonium, and IKM4 activated by 4-aminopyridine. The relatively specific muscarinic receptors subtype antagonists methoctramine (M2), and tropicamide (M4) inhibited both current components induced by bethanechol, suggesting a lack of specificity of these antagonists on cat atrial myocytes. The specific antagonist of M3 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 M3 receptors are probably not involved in the bethanechol action. The IK(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 IK(ACh).
KeywordsBethanechol Feline atrial myocytes Muscarinic inward rectifying potassium current Muscarinic receptors
We thank Dr. Michael Sanguinetti for critical reading of the manuscript. This work was supported by Consejo Nacionl de Ciencia y Tecnologia (CONACyT, México) grant 35136-N (to RANP) and grant 41536-M (to JASCh). These experiments were approved by the Ethics Committee of the University of Colima, Colima, Col., México.
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