Increased colonic motility in a rat model of irritable bowel syndrome is associated with up-regulation of L-type calcium channels in colonic smooth muscle cells.
OBJECTIVE
This paper aimed to investigate the relationship between up-regulation of L-type calcium channels and altered motility disorder in a rat model of irritable bowel syndrome (IBS).


METHODS
Male Sprague-Dawley rats were subjected to neonatal maternal separation (NMS) from postnatal day 2-14 or normal handling (NH), and used when weighted 250-300 g. Colonic smooth muscle contractions was studied in an organ bath system. L-type Ca(2+) channel alpha(1c) subunit expression in smooth muscles from rat colon were studied by immunofluorescence and Western blotting analysis. The intracellular calcium concentration ([Ca(2+)](i)) of enzymatically isolated single colonic smooth muscle cell was studied with laser confocal fluorescent microscopy.


RESULTS
The fecal pellets during 1 h water avoidance stress (WAS) were significantly increased; the amplitude of spontaneous contractions and contractions induced by Bay K 8644 (10 nM-1 microM), KCl (10-60 mM) and ACh (100 nM-10 microM) were significantly increased in NMS rats, when comparing with that of NH rats. [Ca(2+)]i induced by Bay K 8644 (1 microM), KCl (40 mM), and ACh (10 microM) significantly increased in muscle cells of NMS rats than NH rats. Further, alpha(1c) protein expression was significantly up-regulated in colonic smooth muscle of NMS rats than NH rats.


CONCLUSIONS
These results suggest that NMS lead to up-regulation of L-type Ca(2+) channels expression in the colon, which contributes to the colonic motility disorder. Our findings provide direct evidence to help understanding the underlying mechanism of chronic stress-induced colonic motility disorder in IBS.
Zhang
M
M
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
Leung
F-P
FP
Huang
Y
Y
Bian
Z-X
ZX
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D043183:Irritable Bowel Syndrome / Q000378:metabolism*; D008297:Male; D008426:Maternal Deprivation; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine; D000109:Acetylcholine