A minor role for Ca2+ sensitization in sustained contraction through activation of muscarinic receptor in circular muscle of rat distal colon

Pflugers Arch. 2007 Jul;454(4):565-74. doi: 10.1007/s00424-007-0221-7. Epub 2007 Feb 23.


We previously demonstrated that Ca(2+) sensitization has an essential role for carbachol-induced contraction in the longitudinal muscle of the rat distal colon. In the present study, we extended these studies to clarify the role of Ca(2+) sensitization in contraction induced by the activation of muscarinic receptors in the circular muscle of the rat distal colon. Carbachol induced a rapid phasic contraction followed by a sustained contraction that was significantly lower than the phasic and was superimposed with the rhythmic contractions. The extent of increase in intracellular Ca(2+) concentration that was measured simultaneously with tension recording was dissociated from the phasic contraction, whereas it exhibited to a similar extent as sustained contraction. In alpha-toxin-permeabilized preparations, Ca(2+) induced contraction comprising a rapid phasic and a subsequent low sustained component. After Ca(2+)-induced sustained contraction reached a constant level, guanosine triphosphate (GTP) addition resulted in the enhancement of contractile force in a concentration-dependent manner. Carbachol in the presence of GTP caused a further minimal increase in tension (Ca(2+) sensitization). Chelerythrine, a protein kinase C (PKC) inhibitor, inhibited carbachol-induced Ca(2+) sensitization but not GTP-induced Ca(2+) sensitization. In contrast, Y-27632, a Rho kinase inhibitor, inhibited GTP-induced Ca(2+) sensitization but not that induced by carbachol. Phorbol 12,13-dibutyrate, a PKC activator, increased the sustained contraction. These results suggest that the activation of muscarinic receptor with carbachol induces Ca(2+) sensitization via activation of PKC, but this action is minor in the circular muscle of the rat distal colon as a result of limited coupling between muscarinic receptors and Ca(2+) sensitization via the PKC pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Amides / pharmacology
  • Animals
  • Benzophenanthridines / pharmacology
  • Calcium / physiology*
  • Carbachol / pharmacology
  • Carcinogens / pharmacology
  • Cholinergic Agonists / pharmacology
  • Colon / drug effects
  • Colon / physiology*
  • Dose-Response Relationship, Drug
  • Guanosine Triphosphate / pharmacology
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle Relaxants, Central
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Phorbol 12,13-Dibutyrate / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Muscarinic / physiology*


  • Alkaloids
  • Amides
  • Benzophenanthridines
  • Carcinogens
  • Cholinergic Agonists
  • Muscle Relaxants, Central
  • Pyridines
  • Receptors, Muscarinic
  • Y 27632
  • Phorbol 12,13-Dibutyrate
  • Guanosine Triphosphate
  • Carbachol
  • chelerythrine
  • Calcium