Zhixuan Wu1, Wei Shen. 1. Department of Gastroenterology, The Second Affiliated Hospital, Chonqing Medical Universtity, Chonqing, China.
Abstract
BACKGROUND AND AIM: The incidence of gallbladder stones is higher in women during pregnancy than in men. Progesterone can inhibit gallbladder motility and facilitate gallstone formation. However, the ionic mechanisms have not been fully illuminated. This study sought to investigate the effects of progesterone on L-type calcium currents and voltage-dependent potassium currents in gallbladder smooth muscle cells. METHODS: Gallbladder smooth muscle cells were isolated by enzymatic digestion from adult guinea pigs. Ionic currents were recorded by the whole-cell patch clamp method. RESULTS: Progesterone inhibited L-type calcium currents in a concentration-dependent manner. The characteristic of current-voltage curve was not significantly altered. The amplitude of calcium currents was gradually suppressed, reached a steady-state level within 4-6 min, and restored partly after washout. In the presence of protein kinase A (PKA) inhibitor, Rp-cAMP, the inhibitory effect induced by progesterone was apparently attenuated, whereas forskolin, a direct activator of adenylate cyclase, could suppress L-type calcium channel. However, progesterone did not significantly affect voltage-dependent potassium currents. CONCLUSIONS: Progesterone inhibits L-type calcium channel by cAMP/PKA pathway in gallbladder smooth muscle cells. This may be an important mechanism for the gallbladder hypomotility induced by progesterone.
BACKGROUND AND AIM: The incidence of gallbladder stones is higher in women during pregnancy than in men. Progesterone can inhibit gallbladder motility and facilitate gallstone formation. However, the ionic mechanisms have not been fully illuminated. This study sought to investigate the effects of progesterone on L-type calcium currents and voltage-dependent potassium currents in gallbladder smooth muscle cells. METHODS: Gallbladder smooth muscle cells were isolated by enzymatic digestion from adult guinea pigs. Ionic currents were recorded by the whole-cell patch clamp method. RESULTS:Progesterone inhibited L-type calcium currents in a concentration-dependent manner. The characteristic of current-voltage curve was not significantly altered. The amplitude of calcium currents was gradually suppressed, reached a steady-state level within 4-6 min, and restored partly after washout. In the presence of protein kinase A (PKA) inhibitor, Rp-cAMP, the inhibitory effect induced by progesterone was apparently attenuated, whereas forskolin, a direct activator of adenylate cyclase, could suppress L-type calcium channel. However, progesterone did not significantly affect voltage-dependent potassium currents. CONCLUSIONS:Progesterone inhibits L-type calcium channel by cAMP/PKA pathway in gallbladder smooth muscle cells. This may be an important mechanism for the gallbladder hypomotility induced by progesterone.