Abstract

Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits, often linked to dysregulated colonic motility. Short-chain fatty acids (SCFAs), such as sodium butyrate, are key microbial metabolites that modulate gut function, but their precise cellular mechanisms in motility regulation remain incompletely understood. This study investigates the role of voltage-gated potassium (KV) and large-conductance calcium-activated potassium (BK) channels in mediating the effects of sodium butyrate on colonic smooth muscle contractility in a mouse model of IBS. Using ex vivo organ bath pharmacology and electrophysiological patch-clamp techniques on isolated colonic smooth muscle cells, we examined the modulatory effects of sodium butyrate on spontaneous and induced contractions. Our findings indicate that sodium butyrate significantly inhibits colon motility, and this effect is substantially attenuated by selective blockers of BK channels, but not KV channels. Mechanistically, sodium butyrate appears to hyperpolarize the smooth muscle cell membrane by directly or indirectly activating BK channels, thereby reducing excitability and contractility. These results highlight the BK channel as a critical membrane-bound target for sodium butyrate in the context of IBS-related motility dysfunction, offering a potential therapeutic pathway for SCFA-based interventions.