Mechanisms of ion channel in irritable bowel syndrome caused by depression induced abnormal colon motility in rats

Abstract

Objective To investigate mechanisms of ion channel in irritable bowel syndrome (IBS) caused by depression induced abnormal colon motility in rats. Methods Adult male SD SPF rats were divided into control group and depression group, 15 rats in each group. The depression models were induced by chronic unpredictable mild stress stimulation. After 28 days, the success of depression model was confirmed by open field test (OFT) and fluid consumption test (FCT). The gastrointestinal reaction was determined by clinical symptoms, fecal character and times.Abdominal contraction reflex threshold was calculated to evaluate the changes of visceral sensitivity after colorectal distention and to determine the incidence of IBS. Single rat colonic myocytes were isolated by enzyme method. The changes of L-type calcium current (ICa-L) and kinetics properties were recorded via whole-cell patch clamp technique. The t test was performed for comparison between two groups and Pearson method was for correlation analysis. Results Compared with control group, the body weight, OFT and FCT of the rats in depression group were significantly decreased. The rats of depression group have severe body weakness symptoms, the particle number and water content of fecal increasing, capacity threshold significantly decreased and which was negative correlated with OFT and FCT (r=-0.89 and 0.91, both P<0.01). The incidence of IBS was 14/15. Compared with control group, ICa-Lof colonic myocytes of rats in depression group was significantly increased, ICa-Lof control group was (-21.31±4.79) pA and that of depression group was (-33.52±4.45) pA, and which was positive correlated with the particle number and water content of fecal of depression rats (r=0.91 and 0.91, both P<0.01). Moreover the current-voltage (I-V) curve of control group was at middle and of depression group was at the bottom. The steady-state activation curve of ICa-L of depression group markedly left shifted, and the maximum half activated voltages decreased from (-7.96±5.95) mV of control group to (-14.81±3.33) mV. Moreover, recovery of inactivation of ICa-Lwas fast, the recovery time of maximum half inactivation was shorten from (393.28±41.79) ms of control group to (163.29±27.34) ms, 58.48% in advance. Conclusions Depression could induce obvious IBS in gastrointestinal of rats. The mechanisms maybe depression causes ICa-Lof colonic myocytes abnormally increasing, steady-state activation gate open in advance, accelerate recovery time of inactivation and ion channel remodeling of ICa-L. Key words: Depression; Colonic smooth muscle cells; L-type calcium current/Kinetics; Irritable bowel syndrome; Electrical remodeling