title: A functional role for small-conductance calcium-activated potassium channels in sensory pathways including nociceptive processes.
abstract: We investigated the role of small-conductance calcium-activated potassium (SK) and intermediate-conductance calcium-activated potassium channels in modulating sensory transmission from peripheral afferents into the rat spinal cord. Subunit-specific antibodies reveal high levels of SK3 immunoreactivity in laminas I, II, and III of the spinal cord. Among dorsal root ganglion neurons, both peripherin-positive (C-type) and peripherin-negative (A-type) cells show intense SK3 immunoreactivity. Furthermore, dorsal root-stimulated sensory responses recorded in vitro are inhibited when SK channel activity is increased with 1-ethyl-2-benzimidazolinone (1-EBIO). In vivo electrophysiological recordings show that neuronal responses to naturally evoked nociceptive and nonnociceptive stimuli increase after application of the selective SK channel blocker 8,14-diaza-1,7(1,4)-diquinolinacyclotetradecaphanedium di-trifluoroacetate (UCL 1848), indicating that SK channels are normally active in moderating afferent input. Conversely, neuronal responses evoked by mechanical stimuli are inhibited when SK channel activity is increased with 1-EBIO. These effects are reversed by the subsequent application of UCL 1848. Our data demonstrate that SK channels have an important role in controlling sensory input into the spinal cord.
authors.affiliation: Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Parmvir K
authors.initials: PK
authors.lastname: Bahia
authors.forename: Rie
authors.initials: R
authors.lastname: Suzuki
authors.forename: David C H
authors.initials: DC
authors.lastname: Benton
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Jowett
authors.forename: Mao Xiang
authors.initials: MX
authors.lastname: Chen
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Trezise
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Dickenson
authors.forename: Guy W J
authors.initials: GW
authors.lastname: Moss
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D004805:Ependyma / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D064531:Peripherins; D010812:Physical Stimulation / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D011806:Quinolinium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D050916:TRPV Cation Channels / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: C414209:8,14-diaza-1,7(1, 4)-diquinolinacyclotetradecaphane; D001562:Benzimidazoles; D002120:Calcium Channel Agonists; D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C578994:PRPH protein, human; D064531:Peripherins; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011806:Quinolinium Compounds; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C102635:1-ethyl-2-benzimidazolinone