Rhythmic spontaneous contractions in the rat proximal colon.
C-kit immunoreactive cells are known to be interstitial cells of Cajal (ICCs), and they generate pacemaker activity of the gastrointestinal tract. Recently a large number of special smooth muscle cells corresponding to c-kit immunoreactive cells were found in the proximal colon of the guinea pig. We learned that the rat proximal colon showed tetrodotoxin-insensitive regular rhythmic spontaneous contractions (RSCs) and hypothesized that RSCs are generated and/or regulated by ICCs. To prove our hypothesis, we investigated whether RSCs are absent in homozygous Ws/Ws mutant rats, since c-kit positive ICCs along the submucosal surface of the circular muscle (ICC(SM)) and myenteric plexus (ICC(MY)) are lacking. In contrast to our hypothesis, we found that RSCs were still present in the proximal colon of the Ws/Ws mutant rats. A recent study has reported that c-kit negative ICC(SM) remains in Ws/Ws mutant rats. Taken together, RSCs may be generated by c-kit negative ICC(SM) in the rat proximal colon. The blockade of sarcoplasmic reticulum Ca(2+)-ATPase by cyclopiazonic acid (CPA) (10(-6)M) or by thapsigargin (10(-6)M) increased the frequency of RSCs. The increasing effects of CPA on the frequency of RSCs were more prominent in Ws/Ws mutant rats than in +/+ rats. We concluded that the functional coordination between c-kit negative ICC(SM) and other mutationally impaired c-kit positive ICC(MY) and ICC(SM) may be required for moderate regulation in the frequency of spontaneous activity.
Yoneda
S
S
Department of Physiology II, Nara Medical University, Kashihara, 634-8521 Japan.
Kadowaki
M
M
Sugimori
S
S
Sekiguchi
F
F
Sunano
S
S
Fukui
H
H
Takaki
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003106:Colon / Q000294:innervation / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009197:Myenteric Plexus / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019284:Thapsigargin / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007211:Indoles; D019284:Thapsigargin; D009529:Nicardipine; D019009:Proto-Oncogene Proteins c-kit; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium; C000543:cyclopiazonic acid