Effect of potassium channel blockers on isolated rat atrium

This study describes a sensitive in vitro assay using isolated right atrium of adult Wistar rats to discover new compounds as K+ channel antagonists. For the purpose, several well-known K+ channel antagonists were investigated and compared with other compounds that modulate cardiac function. Potassium channel antagonists used in this study were barium chloride (BaCl2), 4-aminopyridine (4-AP), tetraethylammonium (TEA), and E-4031. The concentration-dependent chronotropic and inotropic effect of K+ channel antagonists were determined under physiological condition and under depressed cardiac condition induced by stimulation of cholinergic M receptor with carbachol. Under physiological conditions, these K+ channel antagonists showed a negative chronotropic and positive inotropic response. When the spontaneous beat rate was decreased by cholinergic stimulation, these agents enhanced the beat rate and the force of contraction simultaneously. Study on new compounds found that agents S94052 and S94056 were similar to the above K+ channel antagonists in functional response. Current and voltage-clamp study demonstrated that both new compounds prolonged the duration of action potential and reduced the steady-state K+ outward currents. The functional study described here can provide a sensitive and reproducible atrium model to discover new K+ channel antagonists. Drug Dev. Res. 39:161–166.