Upregulation of L-type calcium channels in colonic inhibitory motoneurons of P/Q-type calcium channel-deficient mice
| Autor: | Xiaochun Bian, Eileen Rodriguez‐Tapia, James J. Galligan, Alberto L. Perez-Medina |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Calcium Channels L-Type Colon Physiology Neuromuscular transmission Neurogastroenterology and Motility Neurotransmission Biology Inhibitory postsynaptic potential Synaptic Transmission Membrane Potentials Calcium Channels Q-Type Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Physiology (medical) Internal medicine medicine Animals L-type calcium channel Q-type calcium channel Gene Myenteric plexus Mice Knockout Motor Neurons Hepatology Gastroenterology Muscle Smooth Calcium Channels P-Type Up-Regulation 030104 developmental biology Endocrinology 030211 gastroenterology & hepatology Gastrointestinal Motility |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 311:G763-G774 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00263.2016 |
| Popis: | 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 α1A 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. |
| Databáze: | OpenAIRE |
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