Role of KV and BK Channels in the Effects of Sodium Butyrate on Colon Motility in a Mouse Model of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a multifactorial disorder, with a high socioeconomic impact, characterized by chronic abdominal pain, bloating, and alterations in bowel habits. The aim of our study was to study the role of voltage gated and large conductance calcium-activated potassium channels in the effect of sodium butyrate on spontaneous and induced by agonists of cholinoreceptors contractions of proximal colon in a mouse model of IBS. IBS was induced by intracolonic infusion of acetic acid in the early postnatal period. The contractile activity of proximal colonic segments was then studied in isometric conditions. The amplitude and frequency of colon contractions were higher in the IBS group. Sodium butyrate demonstrated an inhibitory effect on the amplitude of spontaneous and cholinoreceptor agonist-induced contractions of colon, with lower efficiency in the IBS group. Application of the inhibitors of voltage gated and large conductance calcium-activated potassium channels (BK channels) revealed that BK channels are involved in the inhibitory effects of sodium butyrate on spontaneous and evoked contractile activity in the control group. In the IBS group, BK inhibitor was not effective to prevent sodium butyrate effects on the amplitude of spontaneous contractions; however, it prevented the inhibitory effects of sodium butyrate on the amplitude of contractions induced by epibatidine. We conclude that the inhibitory effects of sodium butyrate on the amplitude of spontaneous and carbachol-/epibatidine-induced contractions are mediated by activation of BK channels of smooth muscle cells or cholinergic terminals. Activation of these channels results in membrane hyperpolarization and a reduction in acetylcholine release with further decreased contractile activity.