Modification by charybdotoxin and apamin of spontaneous electrical and mechanical activity of the circular smooth muscle of the guinea-pig stomach.
1. The effects of charybdotoxin and apamin, putative blockers of Ca(2+)-activated K+ channels, on spontaneous electrical and mechanical activity of circular smooth muscle of the guinea-pig stomach antrum were examined in the presence of 1 microM tetrodotoxin and 1 microM atropine. 2. Both charybdotoxin (> 3 nM) and apamin (> 3 nM) dose-dependently increased the amplitude of spontaneous contractions without altering their frequency. The maximum effect of charybdotoxin was much greater than that of apamin. Both toxins increased the amplitude of intracellular Ca2+ oscillations measured with fura-2. 3. When the extracellular Ca2+ concentration was lowered to 1.5 mM or less, apamin did not significantly potentiate the contractions whereas charybdotoxin still potentiated them but with less potency. 4. Charybdotoxin (30 nM) increased the amplitude of spikes and slow waves, and slightly decreased the resting membrane potential. On the other hand, apamin (100 nM) preferentially increased the slow wave amplitude with no effect on the resting membrane potential. 5. These results suggest that both toxins affect the spontaneous contraction by modifying the electrical activity and that charybdotoxin-sensitive K+ channels and apamin-sensitive ones are differently involved in the spontaneous electrical activity.
Suzuki
K
K
Department of Veterinary Pharmacology, Faculty of Agriculture, Miyazaki University, Japan.
Ito
K M
KM
Minayoshi
Y
Y
Suzuki
H
H
Asano
M
M
Ito
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D018999:Charybdotoxin; D003600:Cytosol / Q000378:metabolism; D004594:Electrophysiology; D016257:Fura-2; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D012604:Scorpion Venoms / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects
D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D001030:Apamin; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2