title: Effect of metabolic inhibition on the excitability of isolated hippocampal CA1 neurons: developmental aspects.
abstract: 1. The effects of brief exposures to hypoxia on the membrane currents of isolated hippocampal CA1 neurons were studied with the use of the whole-cell variation of the patch-clamp technique. Neurons were acutely dissociated from immature (day 2-7) and mature (day 21-43) rats. 2. In the current-clamp mode, Na-cyanide (CN) hyperpolarized both mature and immature neurons. In the voltage-clamp mode, CN decreased the magnitude of the hyperpolarizing holding current in both age groups. 3. CN did not have a consistent effect on the voltage-dependent calcium and potassium currents of immature and mature CA1 neurons but decreased the voltage-dependent inward current of neurons at both ages. This effect was age dependent: the inward current of immature neurons decreased by only 10%, but that of mature neurons decreased by approximately 40%. 4. The decrease in the magnitude of the hyperpolarizing holding current and the depression of the voltage-dependent inward current of mature neurons were observed during brief exposure to N2 (PO2 = 0), indicating that the electroresponses observed with CN were the result of blocking oxidative respiration. 5. The hypoxia-sensitive inward current was blocked by tetrodotoxin (TTX) but was not blocked by cadmium or cesium + tetraethylammonium (TEA). Therefore this current was identified as the voltage-dependent, fast-inactivating sodium current (INa). 6. The isolated sodium current was studied with the use of cadmium to block calcium and TEA + cesium to block potassium currents. In mature neurons, CN left-shifted the steady-state inactivation curve for INa and slowed the deactivation kinetics of INa. CN caused little or no change in INa activation, fast inactivation, recovery from inactivation, or current-voltage (I-V) relationship. 7. We conclude that brief exposures to CN and hypoxia alter the intrinsic excitability of CA1 neurons by at least two mechanisms: 1) alterations in leakage currents and 2) alterations in the fast Na+ conductance that are maturationally dependent. We propose that the alterations in the Na+ conductance may play an adaptive role by reducing O2 demands and thus possibly delaying neuronal injury.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510.
authors.forename: T R
authors.initials: TR
authors.lastname: Cummins
authors.forename: D F
authors.initials: DF
authors.lastname: Donnelly
authors.forename: G G
authors.initials: GG
authors.lastname: Haddad
mesh_terms: D000375:Aging; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia; D002586:Cesium / Q000494:pharmacology; D004594:Electrophysiology / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012966:Sodium Cyanide / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D002586:Cesium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D012966:Sodium Cyanide