R‐type Ca²⁺ Channels Contribute to Neural Control of Murine Colonic Motility

Abstract

BackgroundThe enteric nervous system controls gastrointestinal motility. Multiple subtypes of voltage‐gated Ca2+channels contribute to neurotransmitter release from enteric neurons.ObjectiveWe tested the hypothesis that R‐type Ca2+channels contribute to enteric neurotransmitter release in the mouse colon.MethodsStudies were done in vivo and in vitro using wild type (WT) and a1E Ca2+ channel (R‐type) knockout (KO) mice. Fecal output was measured in vivo. The colonic migrating motor complex (CMMC) was measured in vitro. We used NiCl2 (50 mM) to block R‐type Ca2+ channels , Ω‐conotoxin (CTX, 0.1 mM) to block N‐type Ca2+ channels and tetrodotoxin (TTX, Na+ channel blocker, 0.3 mM) on CMMCs.ResultsThere was no significant difference in fecal output between a1E KO and WT mice. There was no difference in the frequency, propagation speed or amplitude of CMMC contractions between colons from WT and a1E KO mice. NiCl2 slightly decreased contraction amplitude in colons from a1E KO and WT mice. CTX and TTX completely blocked neurogenic contractions and disrupted the CMMC pattern, leaving only spontaneous myogenic contractions behind.ConclusionThese results suggest that either R‐type Ca2+ channels have a minor role in controlling colonic motility, or that there is compensatory upregulation of other Ca2+ types in the constitutive a1E KO mice.*Supported by: R01DK094932