Details

Autor(en) / Beteiligte

• Kölbel, C B
• Holtmann, G
• Mcroberts, J A
• Schöler, S
• Aengenvoordt, P
• Singer, M V
• Mayer, E A

Titel

Involvement of chloride channels in the receptormediated activation of longitudinal colonic muscle

Ist Teil von

• Neurogastroenterology and motility, 1998-12, Vol.10 (6), p.489-498

Ort / Verlag

Oxford UK: Blackwell Science Ltd

Erscheinungsjahr

1998

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• In gastrointestinal smooth muscle, intracellular Cl– is maintained at levels higher than its electrochemical equilibrium. Therefore, Cl– efflux through receptor‐mediated opening of Cl– channels should result in membrane depolarization and may be sufficient to activate voltage‐sensitive calcium channels (VSCCs). To determine the contribution of Cl– channels to receptor‐mediated contraction of the longitudinal muscle layer of the rabbit distal colon, we studied the mechanical response of muscle strips to substance P, carbachol and potassium depolarization following the depletion of Cl–i, and in the presence of the Cl– channel blocker 5‐nitro‐2‐(3‐phenylpropylamino)‐benzoate (NPPB). A 60‐min incubation of tissues in a HEPES‐buffered solution in which NaCl had been replaced by Na isethionate (or Na gluconate) in equimolar amounts resulted in disappearance of phasic contractions, and in a partially reversible reduction of the tonic response to substance P and carbachol, but not to KCl depolarization. When the agonist was applied to tissues in control solution, or to Cl–‐depleted tissues in a solution in which Na+ was acutely replaced in equimolar amounts by N‐methyl‐ D‐glucosamine, the mechanical response to substance P and carbachol was almost abolished. Acute Na+ replacement alone without prior Cl– depletion did not abolish phasic contractions, but reduced the tonic response to substance P and carbachol. Similar to the effect of Cl– depletion, incubation of tissues in NPPB (6.6 × 10–5M) reduced the tonic response to substance P and carbachol, and abolished phasic contractions. These findings are consistent with a contribution of a Cl– channel to the receptor‐mediated activation of colonic smooth muscle. In addition, the data suggest that␣transient Cl– channel mediated depolarizations may play a role in the generation of phasic contractions.