Anoxia on slow inward currents of immature hippocampal neurons.
1. The effects of brief anoxia (2-4 min) on membrane currents--especially the tetrodotoxin (TTX)-insensitive, Cd2+-sensitive slow inward currents, presumed to be Ca2+ currents--were studied by single-electrode voltage clamp in CA1 and CA3 neurons in submerged hippocampal slices from adult and newborn Wistar rats (PN1-13). 2. In mature neurons, anoxia had no effect on Q-type inward relaxations, but slowly activating C-type outward currents were depressed. The most striking change was the suppression of Ca inward currents (especially the slowly inactivating L-type, by greater than 95%). This effect of anoxia was not sensitive to the N-methyl-D-aspartate (NMDA) receptor blocker, D-aminophosphonovalerate. Anoxia also reversibly abolished the NMDA-evoked inward current. 3. In neurons from newborn animals (PN1-6), Q-type inward relaxations and postanoxic outward currents were very small or undetectable. The slow inward (Ca) currents were smaller than in mature cells, but they showed a clearer separation between low-threshold, fast-inactivating and high-threshold, slowly inactivating currents. Both types of current were more resistant to anoxia (mean depression of L-type was by only 53.3 +/- 5.6%, mean +/- SE). 4. In such immature neurons, the NMDA-evoked inward currents were also more resistant to anoxia. 5. By PN7-13, increasing maturation was reflected in 1) larger voltage-dependent inward currents, 2) increasingly evident Q-type relaxations and postanoxic outward currents, and 3) near-complete blockade of inward currents by anoxia (at PN11-13, mean depression of L-type currents was by 98.5 +/- 1.5%).
Krnjević
K
K
Unité 29, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Cherubini
E
E
Ben-Ari
Y
Y
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001224:Aspartic Acid / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D004553:Electric Conductivity; D006624:Hippocampus / Q000254:growth & development* / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D016202:N-Methylaspartate; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D015220:Calcium Channels; D001224:Aspartic Acid; D016202:N-Methylaspartate