Reversible effects of hypoxia on neurons in mouse dorsal root ganglia in vitro.
Mouse dorsal root ganglia (DRG) were isolated and maintained in a tissue chamber. Membrane potential of 'A-type' neurons was recorded with intracellular electrodes. When the supply of oxygen was reduced, cells depolarized by a few mV and then maintained a stable membrane potential or partially repolarized. During depolarization the action potential was reduced in amplitude and the hyperpolarizing afterpotential was depressed. Reoxygenation within 15-88 min was followed by a brief period of hyperpolarization and then complete recovery. In about 60% of the cells, invasion of the cell soma by impulses triggered by dorsal root (DR) stimulation failed during hypoxia while action potentials could still be evoked by stimulation of the peripheral nerve and by direct intracellular stimuli. Conduction from DR into the peripheral nerve stump was unchanged indicating that the blockade of DR-evoked impulse conduction occurred at the bifurcation of the axon. Results with paired pulse stimulation indicated that impulses passing the axon bifurcation leave a long lasting (greater than or equal to 25 ms) post-spike subnormal period. In DRG cells treated with tetraethylammonium (TEA) the calcium-mediated 'shoulder' of the action potential was curtailed during oxygen withdrawal. In contrast to CNS neurons, DRG cells did not show early hypoxic hyperpolarization, nor the delayed hypoxic spreading depression-like depolarization. The findings support the suggestion that the reversible depression of synaptic potentials in the CNS during the early phase of hypoxia is caused by a combination of conduction failure at axon branch points and curtailment of voltage calcium currents of presynaptic terminals, both effects resulting in reduced transmitter output.
Division of Physiology, Duke University Medical Center, Durham, NC 27710.
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D000200:Action Potentials; D000332:Aerobiosis; D000693:Anaerobiosis; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials; D005727:Ganglia, Spinal / Q000502:physiology*; D000860:Hypoxia; D066298:In Vitro Techniques; D008564:Membrane Potentials; D051379:Mice; D009474:Neurons / Q000502:physiology*