Action of dexmedetomidine on the substantia gelatinosa neurons of the rat spinal cord.
Dexmedetomidine is a highly specific, potent and selective alpha(2)-adrenoceptor agonist. Although intrathecal and epidural administration of dexmedetomidine has been found to produce analgesia, whether this analgesia results from an effect on spinal cord substantia gelatinosa (SG) neurons remains unclear. Here, we investigated the effects of dexmedetomidine on postsynaptic transmission in SG neurons of rat spinal cord slices using the whole-cell patch-clamp technique. In 92% of the SG neurons examined (n = 84), bath-applied dexmedetomidine induced outward currents at -70 mV in a concentration-dependent manner, with the value of effective concentration producing a half-maximal response (0.62 microM). The outward currents induced by dexmedetomidine were suppressed by the alpha(2)-adrenoceptor antagonist yohimbine, but not by prazosin, an alpha(1)-, alpha(2B)- and alpha(2C)-adrenoceptor antagonist. Moreover, the dexmedetomidine-induced currents were partially suppressed by the alpha(2C)-adrenoceptor antagonist JP-1302, while simultaneous application of JP-1302 and the alpha(2A)-adrenoceptor antagonist BRL44408 abolished the current completely. The action of dexmedetomidine was mimicked by the alpha(2A)-adrenoceptor agonist oxymetazoline. Plots of the current-voltage relationship revealed a reversal potential at around -86 mV. Dexmedetomidine-induced currents were blocked by the addition of GDP-beta-S [guanosine-5'-O-(2-thiodiphosphate)] or Cs+ to the pipette solution. These findings suggest that dexmedetomidine hyperpolarizes the membrane potentials of SG neurons by G-protein-mediated activation of K+ channels through alpha(2A)- and alpha(2C)-adrenoceptors. This action of dexmedetomidine might contribute, at least in part, to its antinociceptive action in the spinal cord.
Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi, Niigata 951-8510, Japan.
Hideaki
H
Ishii
Tatsuro
T
Kohno
Tomohiro
T
Yamakura
Miho
M
Ikoma
Hiroshi
H
Baba
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013376:Substantia Gelatinosa / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D015221:Potassium Channels; D020927:Dexmedetomidine; D019204:GTP-Binding Proteins