title: Isoflurane modulates neuronal excitability of the nucleus reticularis thalami in vitro.
abstract: The thalamus has a key function in processing sensory information, sleep, and cognition. We examined the effects of a common volatile anesthetic, isoflurane, on modulation of neuronal excitability in reticular thalamic nucleus (nRT) in intact brain slices from immature rats. In current-clamp recordings, isoflurane (300-600 micromol/L) consistently depolarized membrane potential, decreased input resistance, and inhibited both rebound burst firing and tonic spike firing modes of nRT neurons. The isoflurane-induced depolarization persisted not only in the presence of tetrodotoxin, but after replacement of Ca(2+) with Ba(2+) ions in external solution; it was abolished by partial replacement of extracellular Na(+) ions with N-methyl-D-glucamine. In voltage-clamp recordings, we found that isoflurane slowed recovery from inactivation of T-type Ca(2+) current. Thus, at clinically relevant concentrations, isoflurane inhibits neuronal excitability of nRT neurons in developing brain via multiple ion channels. Inhibition of the neuronal excitability of thalamic cells may contribute to impairment of sensory information transfer in the thalamocortical network by general anesthetics. The findings may be important for understanding cellular mechanisms of anesthesia, such as loss of consciousness and potentially damaging consequences of general anesthetics on developing mammalian brains.
authors.affiliation: Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
authors.forename: Pavle M
authors.initials: PM
authors.lastname: Joksovic
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Todorovic
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D020644:Midline Thalamic Nuclei / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane