Regulators involved in the electrically stimulated response of feline esophageal smooth muscle.
In this study, we investigated the components of electrical field stimulation (EFS)-induced responses and the intracellular factors that mediate electrically stimulated responses in feline distal esophageal smooth muscles. Muscle contractions were recorded using an isometric force transducer. Low-frequency EFS induced only off-contraction, but induced on-contraction in the presence of N(G)-nitro-L-arginine methyl ester, suggesting that nitric oxide acts as an inhibitory mediator in smooth muscle. The excitatory composition of both contractions was cholinergic, because of their abolishment by tetrodotoxin or atropine. The off-contraction was abolished in Ca(2+)-free buffer but reappeared in normal Ca(2+)-containing buffer. ML-9, a myosin light chain kinase (MLCK) inhibitor, significantly inhibited off-contraction, whereas chelerythrine (protein kinase C inhibitor) did not affect the contraction. Aluminum fluoride (a G-protein activator) increased off-contraction. Pertussis toxin (a G(i/o) inactivator) and C3 exoenzyme (a RhoA inactivator) significantly decreased off-contraction. Furthermore, 4-aminopyridine (4-AP), voltage-dependent K(+) (K(v)) channel blocker, did not significantly enhance off-contraction. These results suggest that cholinergic nerves and nitric oxide are major intrinsic contributors to the control of feline distal esophageal smooth muscle motility, and that endogenous cholinergic contractions activated directly by low-frequency EFS may be mediated by external Ca(2+), MLCK, and G proteins, such as G(i/o) and RhoA. Furthermore, our findings suggest that K(+) current via 4-AP-sensitive K(+) (including K(v)) channels is not a major participant in the endogenous cholinergic contractions induced by EFS in feline distal esophageal smooth muscle.
Park
Sun Young
SY
Department of Pharmacology, College of Pharmacy, University of Chung-Ang, Seoul 156-756, Republic of Korea.
Park
Sung Uk
SU
Sohn
Uy Dong
UD
D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D002415:Cats; D018680:Cholinergic Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects / Q000201:enzymology / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism / Q000502:physiology
D018680:Cholinergic Antagonists; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D011950:Receptors, Cholinergic; D009569:Nitric Oxide; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D019204:GTP-Binding Proteins; D000109:Acetylcholine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester