The Journal of Neurophysiology Vol. 80 No. 5 November 1998, pp. 2378-2390
Copyright ©1998 The American Physiological Society

Potassium Conductance Causing Hyperpolarization of CA1 Hippocampal Neurons During Hypoxia

G. Erdemli, Y. Z. Xu, and K. Krnjevi

Anaesthesia Research Department, McGill University, Montreal, Quebec H3G 1Y6, Canada

Erdemli, G., Y. Z. Xu, and K. Krnjevi. Potassium conductance causing hyperpolarization of CA1 hippocampal neurons during hypoxia. J. Neurophysiol. 80: 2378-2390, 1998. In experiments on slices (from 100- to 150-g Sprague-Dawley rats) kept at 33°C, we studied the effects of brief hypoxia (2-3 min) on CA1 neurons. In whole cell recordings from submerged slices, with electrodes containing only KMeSO₄ and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid, and in the presence of kynurenate and bicuculline (to minimize transmitter actions), hypoxia produced the following changes: under current clamp, 36 cells were hyperpolarized by 2.7 ± 0.5 (SE) mV and their input resistance (R_in) fell by 23 ± 2.7%; in 30 cells under voltage clamp, membrane current increased by 114 ± 22.3 pA and input conductance (G_in) by 4.9 ± 0.9 nS. These effects are much greater than those seen previously with K gluconate whole cell electrodes, but only half those seen with "sharp" electrodes. The hypoxic hyperpolarizations (or outward currents) were not reduced by intracellular ATP (1-5 mM) or bath-applied glyburide (10 µM): therefore they are unlikely to be mediated by conventional ATP-sensitive K channels. On the other hand, their depression by internally applied ethylene glycol-bis-(-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1.1 and 11 mM) and especially 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (11-33 mM) indicated a significant involvement of Ca-dependent K (K_Ca) channels. The -adrenergic agonist isoprenaline (10 µM) reduced hypoxic hyperpolarizations and decreases in R_in (n = 4) (and in another 11 cells corresponding changes in G_in); and comparable but more variable effects were produced by internally applied 3':5'-adenosine cyclic monophosphate (cAMP, 1 mM, n = 6) and bath-applied 8-bromo-cAMP (n = 8). Thus afterhyperpolarization-type K_Ca channels probably take part in the hypoxic response. A major involvement of G proteins is indicated by the near total suppression of the hypoxic response by guanosine 5'-O-(3-thiotriphosphate) (0.1-0.3 mM, n = 23) and especially guanosine 5'-O-(2-thiodiphosphate) (0.3 mM, n = 26), both applied internally. The adenosine antagonist 8-(p-sulfophenyl)theophylline (10-50 µM) significantly reduced hypoxic hyperpolarizations and outward currents in whole cell recordings (with KMeSO₄ electrodes) from submerged slices but not in intracellular recordings (with KCl electrodes) from slices kept at gas/saline interface. In further intracellular recordings, antagonists of -aminobutyric acid-B or serotonin receptors also had no clear effect. In conclusion, these G-protein-dependent hyperpolarizing changes produced in CA1 neurons by hypoxia are probably initiated by Ca²⁺ release from internal stores stimulated by enhanced glycolysis and a variable synergistic action of adenosine.

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