title: Muscarinic activation of transient inward current and contraction in canine colon circular smooth muscle cells.
abstract: Muscarinic receptor mediated membrane currents and contractions were studied in isolated canine colon circular smooth muscle cells. Carbachol (10(-5) M) evoked a slow transient inward current that was superimposed by a transient outward current at holding potentials greater than -50 mV. Carbachol contracted the cells by 70 +/- 2%. The effects of carbachol were blocked by atropine (10(-6) M), tetraethyl ammonium (20 mM), and BAPTA-AM (25 mM applied for 20 min). The inward current and contraction were not sensitive to diltiazem (10(-5) M), nitrendipine (3 x 10(-7) M), niflumic acid (10(-5) M), or N-phenylanthranilic acid (10(-4) M), but were gradually inhibited after repetitive stimulations in Ca2+ free solution. Ni2+ (2 mM) inhibited the inward current by 67 +/- 4%. The inward current reversed at +15 mV. The outward component could be selectively inhibited by iberiotoxin (20 nM) or by intracellular Cs+. Repeated stimulation in the presence of cyclopiazonic acid (CPA, 3 microM) inhibited the carbachol-induced outward current and partially inhibited contraction. CPA did not inhibit the inward current. In conclusion, muscarinic receptor stimulation evoked a CPA-sensitive calcium release that caused contraction and a CPA-insensitive transient inward current was activated that is primarily carried by Ca2+ ions and is sensitive to Ni2+.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Molleman
authors.forename: L W
authors.initials: LW
authors.lastname: Liu
authors.forename: J D
authors.initials: JD
authors.lastname: Huizinga
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D014118:Toxins, Biological / Q000494:pharmacology
chemical_list: D007211:Indoles; D007473:Ion Channels; D018721:Muscarinic Agonists; D010455:Peptides; D011976:Receptors, Muscarinic; D014118:Toxins, Biological; C064719:iberiotoxin; D002217:Carbachol; D002118:Calcium; C000543:cyclopiazonic acid