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Publication : Upregulation of L-type calcium channels in colonic inhibitory motoneurons of P/Q-type calcium channel-deficient mice.

First Author  Rodriguez-Tapia E Year  2016
Journal  Am J Physiol Gastrointest Liver Physiol Volume  311
Issue  4 Pages  G763-G774
PubMed ID  27586650 Mgi Jnum  J:240439
Mgi Id  MGI:5883396 Doi  10.1152/ajpgi.00263.2016
Citation  Rodriguez-Tapia E, et al. (2016) Upregulation of L-type calcium channels in colonic inhibitory motoneurons of P/Q-type calcium channel-deficient mice. Am J Physiol Gastrointest Liver Physiol 311(4):G763-G774
abstractText  Enteric inhibitory motoneurons use nitric oxide and a purine neurotransmitter to relax gastrointestinal smooth muscle. Enteric P/Q-type Ca2+ channels contribute to excitatory neuromuscular transmission; their contribution to inhibitory transmission is less clear. We used the colon from tottering mice (tg/tg, loss of function mutation in the alpha1A pore-forming subunit of P/Q-type Ca2+ channels) to test the hypothesis that P/Q-type Ca2+ channels contribute to inhibitory neuromuscular transmission and colonic propulsive motility. Fecal pellet output in vivo and the colonic migrating motor complex (ex vivo) were measured. Neurogenic circular muscle relaxations and inhibitory junction potentials (IJPs) were also measured ex vivo. Colonic propulsive motility in vivo and ex vivo was impaired in tg/tg mice. IJPs were either unchanged or somewhat larger in tissues from tg/tg compared with wild-type (WT) mice. Nifedipine (L-type Ca2+ channel antagonist) inhibited IJPs by 35 and 14% in tissues from tg/tg and WT mice, respectively. The contribution of N- and R-type channels to neuromuscular transmission was larger in tissues from tg/tg compared with WT mice. The resting membrane potential of circular muscle cells was similar in tissues from tg/tg and WT mice. Neurogenic relaxations of circular muscle from tg/tg and WT mice were similar. These results demonstrate that a functional deficit in P/Q-type channels does not alter propulsive colonic motility. Myenteric neuron L-type Ca2+ channel function increases to compensate for loss of functional P/Q-type Ca2+ channels. This compensation maintains inhibitory neuromuscular transmission and normal colonic motility.
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