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KCNQ/M currents in sensory neurons: Significance for pain therapy

Passmore, GM; Selyanko, AA; Mistry, M; Al-Qatari, M; Marsh, SJ; Matthews, EA; Dickenson, AH; ... Brown, DA; + view all (2003) KCNQ/M currents in sensory neurons: Significance for pain therapy. J NEUROSCI , 23 (18) 7227 - 7236. Green open access

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Abstract

Neuronal hyperexcitability is a feature of epilepsy and both inflammatory and neuropathic pain. M currents [I-K(M)] play a key role in regulating neuronal excitability, and mutations in neuronal KCNQ2/3 subunits, the molecular correlates of I-K(M), have previously been linked to benign familial neonatal epilepsy. Here, we demonstrate that KCNQ/M channels are also present in nociceptive sensory systems. I-K(M) was identified, on the basis of biophysical and pharmacological properties, in cultured neurons isolated from dorsal root ganglia (DRGs) from 17-d-old rats. Currents were inhibited by the M-channel blockers linopirdine (IC50, 2.1 muM) and XE991 (IC50, 0.26 muM) and enhanced by retigabine (10 muM). The expression of neuronal KCNQ subunits in DRG neurons was confirmed using reverse transcription-PCR and single-cell PCR analysis and by immunofluorescence. Retigabine, applied to the dorsal spinal cord, inhibited C and Adelta fiber-mediated responses of dorsal horn neurons evoked by natural or electrical afferent stimulation and the progressive "windup" discharge with repetitive stimulation in normal rats and in rats subjected to spinal nerve ligation. Retigabine also inhibited responses to intrapaw application of carrageenan in a rat model of chronic pain; this was reversed by XE991. It is suggested that I-K(M) plays a key role in controlling the excitability of nociceptors and may represent a novel analgesic target.

Type: Article
Title: KCNQ/M currents in sensory neurons: Significance for pain therapy
Identifier: PMID: 12904483
Open access status: An open access version is available from UCL Discovery
Keywords: M-current, dorsal root ganglion, neuropathic pain, retigabine, KCNQ, nociceptors, KCNQ1-4 POTASSIUM CHANNELS, ANTICONVULSANT RETIGABINE, FUNCTIONAL EXPRESSION, SYMPATHETIC NEURONS, LINOPIRDINE DUP-996, NEUROPATHIC PAIN, K+ CHANNELS, RAT, KCNQ2/KCNQ3, EPILEPSY
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/9493
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