Spontaneous activity of guinea pig ileum longitudinal muscle regulated by Ca(2+)-activated K+ channel.
Isolated guinea pig ileum displayed spontaneous contraction and fluctuation of membrane potential originating from the longitudinal muscle. Transmural stimulation of the enteric nerve plexus evoked contractions that were followed by lowered muscle tone and decreased spontaneous activity. The Na+ channel blocker tetrodotoxin, N-type Ca2+ channel blockers omega-conotoxins GVIA and MVIIA, the muscarinic receptor antagonist atropine, and inhibitory mediators alpha, beta-methylene-ATP and sodium nitroprusside all inhibited stimulation-evoked contraction while restoring spontaneous motility. L-type Ca2+ channel blockers nifedipine and calciseptine completely suppressed evoked and spontaneous contractions. Blockade of the large-conductance Ca(2+)-activated K+ (Kca) channel with charybdotoxin (but not of small-conductance Kca channel by apamin or of ATP-regulated K+ channel by glybenclamide) induced spikelike depolarization, inhibited nerve stimulation-evoked membrane hyperpolarization, and increased spontaneous activity. The results suggest that the large-conductance Kca channel is constitutively activated for modulations of spontaneous activity, and that muscle excitation, through elevation of Ca2+ levels, stimulates the large-conductance Kca channel to suppress spontaneous activity.
Hong
S J
SJ
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei.
Roan
Y F
YF
Chang
C C
CC
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology*; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology*; D008564:Membrane Potentials; D009130:Muscle, Smooth / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D010276:Parasympatholytics; D010455:Peptides; D015221:Potassium Channels; D020960:omega-Conotoxins; D013779:Tetrodotoxin; D001285:Atropine; C078452:ziconotide; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester