Nitric oxide may be a mediator of effects of prolonged but not brief anoxia in CA1 neurons in slices

Abstract

As a known vasodilator, nitric oxide (NO) probably acts by hyperpolarizing smooth muscle by increasing K conductance (G K). Therefore NO could mediate the anoxic hyperpolarizations of brain neurons that are also mediated by G K. We investigated this question by recording from CA1 neurons in submerged hippocampal slices (from rats), kept at 33 °C. Incubation with the NO synthase inhibitor N ω-nitro- l-arginine methyl ester ( l-NAME; 200 μM) had no significant effect on CA1 population spikes ( Δ = 2.5%, SEM ± 3.1%, n = 7) or on the time course of their suppression by brief exposure to anoxia (2–3 min). In intracellular recordings, l-NAME did not change the resting membrane potential or input resistance ( n = 10). In the presence of l-NAME, anoxic changes were not significantly different: the cells were hyperpolarized by 6.4 ± 0.74 mV (6.3 ± 0.82mV for controls) and their resistance decreased by 16 ± 3.2% (18 ± 1.4% for controls, n = 10). In whole-cell recordings from another 15 cells (clamped at ≈ − 50 mV, near resting level), l-NAME also had no consistent effect on input conductance (G N) or holding current (I H); and the anoxic increases in G N were unchanged (44 ± 12% before and 48 ± 20% after, for n = 10). Thus, NO does not appear to be a significant element in the mechanism of membrane and synaptic changes during brief anoxia in CA1 neurons in slices. In partial agreement with previous findings, however, in 11 pairs of slices exposed to much longer anoxia (8–45 min), l-NAME tended to increase either the probability of the speed or postanoxic recovery of population spikes. Anoxic production of NO may therefore contribute to neuronal dysfunction caused by prolonged (but not brief) anoxia.