The influence of ouabain on twitch contractions in the presence of veratridine.
1. Direct stimulation evoked twitches in mouse diaphragm muscles in presence of 10 microM D-tubocurarine in vitro. Effects of ouabain and their dependence on K+ were examined on the twitch responses and action potentials in the presence and absence of twitch potentiators. 2. Ouabain inhibited twitch contractions only in the presence of veratridine, aconitine and monensin while it had no inhibitory effect on control twitches. The interactions between ouabain and these twitch potentiators depended on the presence of external K+, except in the case of monensin. 3. Removal of Ca2+ from a bathing solution accelerated the potentiating effect of veratridine and the antagonizing effect of ouabain. 4. Caffeine further potentiated the twitches which had been attenuated by ouabain combined with veratridine. 5. Ouabain combined with veratridine consistently decreased resting membrane potentials, action potentials and overshoot potentials and prolonged time to peak of and duration of the muscle action potentials. 6. Tetraethylammonium, 4-aminopyridine, and caffeine produced twitch potentiation which was insensitive to ouabain or the removal of K+. 7. These results suggest that twitch contractions in the presence of activators of sodium channels link with activation of Na+-K+-ATPase. Accumulation of Na+ inside the muscle fibres may uncouple the excitation-contraction system. 8. This uncoupling may not include the caffeine-sensitive process that controls the release of Ca2+ from the sarcoplasmic reticulum. Na+ accumulation may decrease transmembraneous gradient of this ions, thereby causing a reduction in excitation coupled with twitch contraction.
Nishimura
M
M
Department of Veterinary Pharmacology, College of Agriculture, University of Osaka Prefecture, Japan.
Ohtani
H
H
Yagasaki
O
O
D015761:4-Aminopyridine; D000157:Aconitine / Q000494:pharmacology; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008985:Monensin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D012132:Respiratory Muscles / Q000187:drug effects*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*
D000631:Aminopyridines; D013757:Tetraethylammonium Compounds; D002110:Caffeine; D010042:Ouabain; D011189:Potassium Chloride; D014701:Veratridine; D008985:Monensin; D015761:4-Aminopyridine; D014702:Veratrine; D014403:Tubocurarine; D000157:Aconitine