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 degr ees C on membrane potential and resting conductance in pyramidal cells from the hippocampal CA1 region in rat brain slices. The initial effect of hypo xia was a gradual hyperpolarization; the peal; change in membrane potential measured over 15 min was -5.3 +/- 0.22 mV (P < 0.0001). After reoxygenatio n 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 restin g conductance. The effect was not influenced by intracellular Cl- concentra tion, which indicated that it was not due to an inward how of Cl- ions. The addition of tolbutamide, glibenclamide and dantrolene sodium did not affec t the hypoxic hyperpolarization, neither did the presence of ATP in the pip ette solution. The presence/absence of glucose in the perfusion medium did not influence the initial hyperpolarization during hypoxia; however, glucos e seemed to prevent the subsequent depolarization under hypoxia. It was concluded that hypoxia caused an initial hyperpolarization of CA1 ce lls which was related to an increase in the resting conductance. The result s did not suggest the involvement of ATP-sensitive K+ channels. (C) 1999 IB RO. Published by Elsevier Science Ltd.