Bile Acid Modulation of Gastroinstinal Smooth Muscle Contraction and Ionic Currents

We have examined whether bile acids can affect the electrical and mechanical activities of circular smooth muscle of canine colon and ileum, using isometric tension measurement or patch clamp technique. It was found that a dilution of canine bile $(0.03{\sim}2%\;by\;volume)$ enhanced or inhibited the amplitude of spontaneous contractions. An individual component of bile, deoxycholic acid (DCA) enhanced the frequency and amplitude of the spontaneous contractile activity at $10^{-6}\;M,$ while DCA at $10^{-4}\;M$ inhibited the contraction. Similarly, the response to cholic acid was excitatory at $10^{-5}\;M$ and inhibitory at $3{\times}10^{-4}\;M.$ Taurocholic acid at $10^{-4}\;M$ enhanced the amplitude of muscle contraction. Electrically, canine bile at 1% reversibly depolarized the colonic myocytes under current clamp mode. Bile acids also elicited non-selective cation currents under voltage clamp studies, where $K^+$ currents were blocked and the $Cl^-$ gradient was adjusted so that $E_{Cl}^-$ was equal to -70 mV, a holding potential. The non-selective cation current might explain the depolarization caused by bile acids in intact muscles. Furthermore, the bile acid regulation of electrical and mechanical activities of intestinal smooth muscle may explain some of the pathophysiological conditions accompanying defects in bile reabsorption.