Evidence map›Paper›PMID 27462070›Full record

ArticlePhysiological reports2016

The role of Cx36 and Cx43 in 4-aminopyridine-induced rhythmic activity in the spinal nociceptive dorsal horn: an electrophysiological study in vitro.

Christopher W P Kay, Daniel Ursu, Emanuele Sher, Anne E King

Open access · goldAbstract read
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Article in Physiological reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

Christopher W P KaySchool of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom.
Daniel UrsuEli Lilly & Co., Lilly Research Centre Erl Wood Manor, Windlesham, Surrey, GU20 6PH, United Kingdom.
Emanuele SherEli Lilly & Co., Lilly Research Centre Erl Wood Manor, Windlesham, Surrey, GU20 6PH, United Kingdom.
Anne E KingSchool of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, United Kingdom a.e.king@leeds.ac.uk.
University of Leeds · GBEli Lilly (United Kingdom) · GBEli Lilly (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Connexin (Cx) proteins and gap junctions support the formation of neuronal and glial syncytia that are linked to different forms of rhythmic firing and oscillatory activity in the CNS. In this study, quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to profile developmental expression of two specific Cx proteins, namely glial Cx43 and neuronal Cx36, in postnatal lumbar spinal cord aged 4, 7, and 14 days. Extracellular electrophysiology was used to determine the contribution of Cx36 and Cx43 to a previously described form of 4-aminopyridine (4-AP)-induced 4-12 Hz rhythmic activity within substantia gelatinosa (SG) of rat neonatal dorsal horn (DH) in vitro. The involvement of Cx36 and Cx43 was probed pharmacologically using quinine, a specific uncoupler of Cx36 and the mimetic peptide blocker Gap 26 which targets Cx43. After establishment of 4-12 Hz rhythmic activity by 4-AP (25 μmol/L), coapplication of quinine (250 μmol/L) reduced 4-AP-induced 4-12 Hz rhythmic activity (P < 0.05). Preincubation of spinal cord slices with Gap 26 (100 μmol/L), compromised the level of 4-AP-induced 4-12 Hz rhythmic activity in comparison with control slices preincubated in ACSF alone (P < 0.05). Conversely, the nonselective gap junction "opener" trimethylamine (TMA) enhanced 4-12 Hz rhythmic behavior (P < 0.05), further supporting a role for Cx proteins and gap junctions. These data have defined a physiological role for Cx36 and Cx43 in rhythmic firing in SG, a key nociceptive processing area of DH. The significance of these data in the context of pain and Cx proteins as a future analgesic drug target requires further study.

Indexed as

4-AminopyridineAnimalsConnexin 43ConnexinsGap Junction delta-2 ProteinGap JunctionsGene Expression Regulation, DevelopmentalLumbar VertebraeMalePotassium Channel BlockersRats, WistarSpinal Cord Dorsal HornSubstantia GelatinosaTissue Culture Techniques4-AminopyridineConnexin 43ConnexinsGap Junction delta-2 ProteinGja1 protein, ratPotassium Channel BlockersConnexinspainrhythmic firingsubstantia gelatinosa

Identifiers

PMID27462070
PMCPMC4962069
OpenAlexW2502211973

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.