Factors influencing an increase in spontaneous transmitter release by hypoxia at the mouse neuromuscular junction.
To test a possibility that the functional buffering of intracellular Ca2+ plays a primary role in the enhancement of spontaneous transmitter release during hypoxia, the frequency of miniature end-plate potentials (m.e.p.p.s) was examined under several conditions. At 36 degrees C, hypoxia (bubbling with 95% N2 and 5% CO2) increased the average frequency of m.e.p.p.s from about 3 s-1 to 100 s-1 or more, in a standard Krebs-Ringer solution. This effect declined with a decrease in the temperature and was much reduced at 24 degrees C. Removal of external Ca2+ (addition of 2 mM-EGTA), increase of Mg2+ levels to 5 mM, and treatment with 20 microM-ouabain, which gave a slight increase, did not reduce the rise in m.e.p.p. frequency during hypoxia. Pre-incubation of the tissue in a solution containing 10 mM-KCl at 24-32 degrees C and its subsequent exposure to hypoxia caused a very marked increase in m.e.p.p. frequency, while incubation in 10 mM-KCl alone caused a small rise in the frequency. These data indicate that this combination potentiates the individual effects of each treatment. These experiments suggest that the hypoxia-induced increase in spontaneous transmitter release is primarily due to an increase in intracellular Ca2+ levels, probably because of inhibition of mechanisms which control buffering and extrusion of intracellular Ca2+. The release and influx mechanisms which elevate intraterminal Ca2+ may also be involved passively in the effect of hypoxia.
Nishimura
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D009469:Neuromuscular Junction / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D018377:Neurotransmitter Agents; D010042:Ouabain; D008274:Magnesium; D011188:Potassium; D010100:Oxygen; D002118:Calcium