RGD Reference Report - TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing. - Rat Genome Database

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TMEM16C facilitates Na(+)-activated K+ currents in rat sensory neurons and regulates pain processing.

Authors: Huang, F  Wang, X  Ostertag, EM  Nuwal, T  Huang, B  Jan, YN  Basbaum, AI  Jan, LY 
Citation: Huang F, etal., Nat Neurosci. 2013 Sep;16(9):1284-90. doi: 10.1038/nn.3468. Epub 2013 Jul 21.
RGD ID: 9681745
Pubmed: PMID:23872594   (View Abstract at PubMed)
PMCID: PMC4034143   (View Article at PubMed Central)
DOI: DOI:10.1038/nn.3468   (Journal Full-text)

TMEM16C belongs to the TMEM16 family, which includes the Ca(2+)-activated Cl(-) channels TMEM16A and TMEM16B and a small-conductance, Ca(2+)-activated, nonselective cation channel (SCAN), TMEM16F. We found that in rat dorsal root ganglia (DRG) TMEM16C was expressed mainly in the IB4-positive, non-peptidergic nociceptors that also express the sodium-activated potassium (K(Na)) channel Slack. Together these channel proteins promote K(Na) channel activity and dampen neuronal excitability. DRG from TMEM16C knockout rats had diminished Slack expression, broadened action potentials and increased excitability. Moreover, the TMEM16C knockout rats, as well as rats with Slack knockdown by intrathecal injection of short interfering RNA, exhibited increased thermal and mechanical sensitivity. Experiments involving heterologous expression in HEK293 cells further showed that TMEM16C modulated the single-channel activity of Slack channels and increased its sodium sensitivity. Our study thus reveals that TMEM16C enhances K(Na) channel activity in DRG neurons and regulates the processing of pain messages.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperalgesia  ISOAno3 (Rattus norvegicus)9681745; 9681745 RGD 
Hyperalgesia  IMP 9681745 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased thermal nociceptive threshold  IMP 9681745 RGD 
hyperresponsive to tactile stimuli  IMP 9681745 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ano3  (anoctamin 3)
Ano6  (anoctamin 6)

Genes (Mus musculus)
Ano3  (anoctamin 3)

Genes (Homo sapiens)
ANO3  (anoctamin 3)


Additional Information