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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Modulation of plateau properties in dorsal horn neurones in a slice preparation of the turtle spinal cord.

1. Modulation of plateau properties in dorsal horn neurones was studied in a transverse slice preparation of the spinal cord of the turtle. In plateau-generating neurones high frequency stimulation of the ipsilateral dorsal root (10-20 Hz, 0.5-2 min) produced a slow depolarization (2.9 +/- 0.6 mV, mean +/- S.E.M.; n = 6) and enhanced the properties mediated by dihydropyridine-sensitive Ca2+ channels. The tetanic stimulus facilitated wind-up and after-discharges even when fast synaptic transmission was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10-20 microM), (+/-)-2-amino-5-phosphonopentanoic acid (AP5, 100 microM), bicuculline (10-20 microM) and strychnine (5-20 microM). 2. Application of cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 10-50 microM) produced a slow depolarization (5.9 +/- 0.5 mV, n = 21) accompanied by an increase in input resistance (28.8 +/- 5.1%, n = 12). 3. ACPD increased the excitability by facilitating the plateau properties. In the presence of tetrodotoxin (TTX, 1 microM) a lower threshold and a slower decay of the plateau potential were observed. These effects resulted in facilitation of wind-up and prolonged after-discharges. 4. All ACPD-induced effects were blocked by alpha-methyl-4-carboxyphenylglycine (MCPG, 0.5-1 mM), a selective antagonist of metabotropic glutamate receptors. The selective agonist for the type I metabotropic glutamate receptor ((RS)-3,5-dihydrophenylglycine (DHPG, 50 microM)) reproduced all the effects of ACPD. 5. Application of a supposed neuromodulator, substance P (1-2 microM) produced a transient depolarization (4 +/- 0.6 mV) lasting 4-6 min during continued application of substance P. Variable effects on the input resistance were observed, a slight increase (12 +/- 2%) being the most frequent. In 61% of the cells, substance P induced a clear increase in excitability with no detectable change in input resistance or membrane potential. 6. The effects of substance P on plateau properties were indistinguishable from those produced by ACPD. Unlike the transient depolarization, the facilitation of the plateau properties persisted in the presence of the agonist. 7. The substance P-induced facilitation of the plateau potential was blocked by GR 82334 (5-10 microM), a selective NK-1 tachykinin-receptor antagonist, and was not affected by MEN 10376 (2 microM), a selective NK-2 antagonist. 8. The facilitation of plateau properties produced by dorsal root stimulation was also reduced by antagonists of metabotropic glutamate receptors and NK-1 tachykinin receptors. 9. We propose that modulation of postsynaptic plateau properties in dorsal horn neurones by activation of type I metabotropic glutamate receptors and NK-1 tachykinin receptors is involved in processing nociceptive information.[1]


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