A functional role for small-conductance calcium-activated potassium channels in sensory pathways including nociceptive processes.
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.
Bahia
Parmvir K
PK
Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom.
Suzuki
Rie
R
Benton
David C H
DC
Jowett
Amanda J
AJ
Chen
Mao Xiang
MX
Trezise
Derek J
DJ
Dickenson
Anthony H
AH
Moss
Guy W J
GW
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
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