Emodin inhibits voltage-dependent potassium current in guinea pig gallbladder smooth muscle.

Emodin is known to prompt bile secretion in gallbladder and to be used in the treatment of cholesterol stones. We studied the effects of emodin on the contraction of gallbladder smooth muscle and voltage-dependent K(+) current in gallbladder smooth muscle cells. Gallbladder muscle strips were obtained from adult guinea pigs and the resting tension was recorded. Gallbladder smooth muscle cells were isolated by enzymatic digestion, and K(+) current was recorded by the whole-cell patch clamp method. Emodin increased the resting tension of gallbladder smooth muscle strips and inhibited voltage-dependent K(+) current in a dose-dependent manner. When 10 microM emodin was applied to gallbladder smooth muscle cells for 3-6 min., the amplitude of voltage-dependent K(+) current was decreased by 31.5 +/- 0.5% at +40 mV, and this inhibitory effect mostly recovered after washout. The steady-state inactivation curves were shifted in a hyperpolarizing direction by emodin. In the presence of the protein kinase C inhibitors staurosporine and chelerythrine, the effect of emodin on voltage-dependent K(+ )current was significantly attenuated. In conclusion, emodin promotes gallbladder contraction, mainly by inhibiting voltage-dependent K(+) current via the protein kinase C pathway. These findings provide theoretical foundation for the application of emodin in gallbladder motility disorders.