Nitric oxide may be a mediator of effects of prolonged but not brief anoxia in CA1 neurons in slices.
As a known vasodilator, nitric oxide (NO) probably acts by hyperpolarizing smooth muscle by increasing K conductance (GK). Therefore NO could mediate the anoxic hyperpolarizations of brain neurons that are also mediated by GK. We investigated this question by recording from CA1 neurons in submerged hippocampal slices (from rats), kept at 33 degrees C. Incubation with the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 200 microM) had no significant effect on CA1 population spikes (delta = 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 +/- 0.82 mV 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 approximately -50 mV, near resting level), L-NAME also had no consistent effect on input conductase (GN) or holding current (IH); and the anoxic increased in GN 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhu
P J
PJ
Anaesthesia Research, Department, McGill University, Montréal, Qu ec, Canada.
Erdemli
G
G
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester