The effects of hypoxia on neuromuscular transmission in a mammalian preparation.
1. The rat diaphragm-phrenic nerve preparation in vitro failed to contract in response to nerve impulses after 10-20 min exposure to solutions containing 95% N(2) and 5% CO(2) (hypoxic solutions) at temperatures between 33 and 38 degrees C. Intracellular recording revealed that end-plate potential (e.p.p.) amplitudes fell below the firing threshold for muscle fibres and then disappeared probably because of block of intramuscular nerve conduction.2. In curarized and Mg-paralysed preparations the reduction in e.p.p. amplitudes was found to be due to a fall in their quantal content. In about half of the Mg-paralysed preparations, however, and in curarized preparations after repeated exposures, there were increases in quantal content of e.p.p.s during hypoxia.3. Miniature end-plate potential (m.e.p.p. frequency increased in a cyclic fashion during hypoxia and this increase was largely suppressed in the presence of a raised extracellular Mg concentration. M.e.p.p. amplitude increased (range 0-100% of control value) after about 20 min hypoxia.4. Post-tetanic potentiation of e.p.p. amplitudes and m.e.p.p. frequency was reduced after exposure to hypoxic solutions. During hypoxia the e.p.p. amplitude potentiation was reduced but the m.e.p.p. frequency potentiation was augmented.5. There was an increase in the post-synaptic sensitivity to carbamylcholine after 20 min hypoxia which was sufficient to explain the increase in m.e.p.p. amplitude. Other post-synaptic changes were a fall in membrane potential (average 6 mV after 20 min) and a fall in membrane resistance after 30-60 min exposure to hypoxia.6. The effects of hypoxia upon neuromuscular transmission were partially explained by reduction of active transport of sodium and potassium ions and consequent depolarization of nerve and muscle.
D000818:Animals; D002245:Carbon Dioxide; D003964:Diaphragm / Q000294:innervation; D004558:Electric Stimulation; D000860:Hypoxia / Q000503:physiopathology*; D008274:Magnesium / Q000494:pharmacology; D009431:Neural Conduction; D009469:Neuromuscular Junction / Q000502:physiology*; D009584:Nitrogen; D010791:Phrenic Nerve / Q000502:physiology; D011199:Potentiometry; D051381:Rats; D014403:Tubocurarine / Q000494:pharmacology
D002245:Carbon Dioxide; D008274:Magnesium; D009584:Nitrogen; D014403:Tubocurarine