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Impaired propulsive motility in the distal but not proximal colon of BK channel β1‐subunit knockout mice
Author(s) -
France M.,
Bhattarai Y.,
Galligan J. J.,
Xu H.
Publication year - 2012
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2012.01981.x
Subject(s) - bethanechol , motility , endocrinology , medicine , bk channel , in vivo , ileum , knockout mouse , chemistry , protein subunit , migrating motor complex , biology , potassium channel , small intestine , microbiology and biotechnology , receptor , biochemistry , muscarinic acetylcholine receptor , gene
Background Large‐conductance Ca 2+ ‐activated K + (BK) channels regulate smooth muscle tone. The BK channel β1‐subunit increases Ca 2+ sensitivity of the α‐subunit in smooth muscle. We studied β1‐subunit knockout (KO) mice to determine if gastrointestinal (GI) motility was altered. Methods Colonic and intestinal longitudinal muscle reactivity to bethanechol and colonic migrating motor complexes (CMMCs) were measured in vitro . Gastric emptying and small intestinal transit were measured in vivo . Colonic motility was assessed in vivo by measuring fecal output and glass bead expulsion time. Myoelectric activity of distal colon smooth muscle was measured in vitro using intracellular microelectrodes. Key Results Bethanechol‐induced contractions were larger in the distal colon of β1‐subunit KO compared to wild type (WT) mice; there were no differences in bethanechol reactivity in the duodenum, ileum, or proximal colon of WT vs β1‐subunit KO mice. There were more retrogradely propagated CMMCs in the distal colon of β1‐subunit KO compared to WT mice. Gastrointestinal transit was unaffected by β1‐subunit KO. Fecal output was decreased and glass bead expulsion times were increased in β1‐subunit KO mice. Membrane potential of distal colon smooth muscle cells from β1‐subunit KO mice was depolarized with higher action potential frequency compared to WT mice. Paxilline (BK channel blocker) depolarized smooth muscle cells and increased action potential frequency in WT distal colon. Conclusions & Inferences BK channels play a prominent role in smooth muscle function only in the distal colon of mice. Defects in smooth muscle BK channel function disrupt colonic motility causing constipation.