Increased calcium influx is responsible for the sustained mechanical tone in colon from dystrophic (mdx) mice.
OBJECTIVE
Proximal colon from dystrophic mice develops spontaneous tone increment, but the mechanisms involved in its development have not been investigated. This study examined whether alterations in the properties of cell membrane calcium channels and/or sarcoplasmic reticular (SR) Ca2+-adenosine triphosphatase (ATPase) contribute to tone development.


METHODS
Effects of calcium-free solution, nifedipine, pinaverium (calcium channel blockers), and cyclopiazonic acid (CPA; SR Ca2+-ATPase inhibitor) on the contractile activity of colon from mdx and control mice were determined.


RESULTS
Calcium-free solution abolished spontaneous contractions in both preparations, but decreased the tone only in mdx mice. Nifedipine or pinaverium abolished phasic contractions, acting with different sensitivities on the 2 preparations. They also decreased the tone in colons of mdx mice, and Ca2+-free solution did not cause any further loss of tone. CPA, after an early contractile effect, abolished spontaneous contractions in control animals. It did not suppress the contractile activity in mdx mice. CPA inhibited the repletion of intracellular calcium stores in both tissues to the same degree.


CONCLUSIONS
Increased Ca2+ influx through L-type voltage-dependent Ca2+ channels seems to be responsible for the sustained mechanical tone of proximal colon from mdx mice. The mechanisms for sequestering calcium appear to be unaltered.
Mulè
F
F
Dipartimento Farmaco-Biologico, Università della Calabria, Arcavacata di Rende, Cs, Palermo, Italy. fmule@mbox.unipa.it
Serio
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003106:Colon / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects; D009136:Muscular Dystrophies / Q000503:physiopathology*; D009543:Nifedipine / Q000494:pharmacology
D007211:Indoles; D009543:Nifedipine; D002118:Calcium; C000543:cyclopiazonic acid