Effect of hypoxia on membrane potential and resting conductance in rat hippocampal neurons.
The present patch-clamp study describes the effect of hypoxia at 30-31 degrees C on membrane potential and resting conductance in pyramidal cells from the hippocampal CA1 region in rat brain slices. The initial effect of hypoxia was a gradual hyperpolarization; the peak change in membrane potential measured over 15 min was -5.3 +/- 0.22 mV (P < 0.0001). After reoxygenation followed a transient hyperpolarization measuring -1.8 +/- 0.24 mV (P < 0.0001) and a subsequent normalization of the membrane potential, which after 5 min did not differ from its level prior to the hypoxic episode. Voltage-clamp analysis showed that the hypoxic hyperpolarization was related to an outward current at the holding potential (-60 mV) and an increase in resting conductance. The effect was not influenced by intracellular Cl- concentration, which indicated that it was not due to an inward flow of Cl- ions. The addition of tolbutamide, glibenclamide and dantrolene sodium did not affect the hypoxic hyperpolarization, neither did the presence of ATP in the pipette solution. The presence/absence of glucose in the perfusion medium did not influence the initial hyperpolarization during hypoxia; however, glucose seemed to prevent the subsequent depolarization under hypoxia. It was concluded that hypoxia caused an initial hyperpolarization of CA1 cells which was related to an increase in the resting conductance. The results did not suggest the involvement of ATP-sensitive K+ channels.
Hyllienmark
L
L
Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm, Sweden.
Brismar
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D015687:Cell Hypoxia; D003620:Dantrolene / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004553:Electric Conductivity; D005905:Glyburide / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D007003:Hypoglycemia; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014044:Tolbutamide / Q000494:pharmacology
D013779:Tetrodotoxin; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D003620:Dantrolene; D005905:Glyburide