title: Cyclic GMP alters the firing rate and thermosensitivity of hypothalamic neurons.
abstract: The rostral hypothalamus, especially the preoptic-anterior hypothalamus (POAH), contains temperature-sensitive and -insensitive neurons that form synaptic networks to control thermoregulatory responses. Previous studies suggest that the cyclic nucleotide cGMP is an important mediator in this neuronal network, since hypothalamic microinjections of cGMP analogs produce hypothermia in several species. In the present study, immunohistochemisty showed that rostral hypothalamic neurons contain cGMP, guanylate cyclase (necessary for cGMP synthesis), and CNG A2 (an important cyclic nucleotide-gated channel). Extracellular electrophysiological activity was recorded from different types of neurons in rat hypothalamic tissue slices. Each recorded neuron was classified according to its thermosensitivity as well as its firing rate response to 2-100 microM 8-bromo-cGMP (a membrane-permeable cGMP analog). cGMP has specific effects on different neurons in the rostral hypothalamus. In the POAH, the cGMP analog decreased the spontaneous firing rate in 45% of temperature-sensitive and -insensitive neurons, an effect that is likely due to cGMP-enhanced hyperpolarizing K(+) currents. This decreased POAH activity could attenuate thermoregulatory responses and produce hypothermia during exposures to cool or neutral ambient temperatures. Although 8-bromo-cGMP did not affect the thermosensitivity of most POAH neurons, it did increase the warm sensitivity of neurons in other hypothalamic regions located dorsal, lateral, and posterior to the POAH. This increased thermosensitivity may be due to pacemaker currents that are facilitated by cyclic nucleotides. If some of these non-POAH thermosensitive neurons promote heat loss or inhibit heat production, then their increased thermosensitivity could contribute to cGMP-induced decreases in body temperature.
authors.affiliation: Department of Physiology & Cell Biology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Chadwick L
authors.initials: CL
authors.lastname: Wright
authors.forename: Penny W
authors.initials: PW
authors.lastname: Burgoon
authors.forename: Georgia A
authors.initials: GA
authors.lastname: Bishop
authors.forename: Jack A
authors.initials: JA
authors.lastname: Boulant
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000502:physiology; D004594:Electrophysiology; D006162:Guanylate Cyclase / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007032:Hypothalamus, Anterior / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C016276:8-bromocyclic GMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP