NITRIC-OXIDE DEPOLARIZES TYPE-II PARAVENTRICULAR NUCLEUS NEURONS IN-VITRO

Nitric oxide is a labile gas which has been implicated in neuronal sig nalling. The enzyme responsible for the production of this molecule is present in the paraventricular nucleus of the hypothalamus, yet a spe cific role for nitric oxide in neurotransmission within this nucleus r emains unclear. Using whole-cell patch-clamp recordings from paraventr icular nucleus neurons in a coronal hypothalamic slice, we have assess ed the acute effects of nitric oxide on membrane potential and ionic c onductance. Recordings were obtained from 78 neurons with epsilon mean resting membrane potential of - 57.8 +/- 0.6 mV and a mean input resi stance of 972 +/- 46 M Omega. Cells were electrophysiologically classi fied into Type I or Type II according to previously established criter ia. Bath application of nitric oxide (delivered either as a gas dissol ved in solution, or liberated from the donor compound, N-acetyl-S-nitr oso-D-penicillamine) elicited reversible membrane depolarizations (3 m V) in 14 of the 19 Type II cells rested. These cells also exhibited a decrease in input resistance following nitric oxide application. Simil ar effects were observed in response to bath application of L-arginine , with 11 of 14 cells displaying depolarizations and accompanying decr eases in input resistance. Inhibition of nitric oxide synthase abolish ed the responses to L-arginine (n=2). The nitric oxide effects persist ed when voltage-activated Na+ channels were blocked by tetrodotoxin (n =6). The depolarizations observed in Type II cells were mimicked by ba th application of a membrane permeable cyclic GMP analogue (8-bromo-cy clic GMP) (n=8). Furthermore, nitric oxide depolarizations were abolis hed by pre-treatment of the slice with the guanylate cyclase inhibitor , LY83583 (n=4). Type I cells did not depolarize in response to nitric oxide (n=11). It is concluded that nitric oxide specifically depolari zes parvocellular neurons within the paraventricular nucleus via a mec hanism that requires activation of guanylate cyclase and subsequent pr oduction of cyclic GMP. These findings provide the first insight into the cellular mechanisms underlying the acute effects of nitric oxide o n neurons in the paraventricular nucleus. (C) 1997 IBRO.