GABA Increases Electrical Excitability in a Subset of Human Unmyelinated Peripheral Axons 英文参考文献.docVIP

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GABA Increases Electrical Excitability in a Subset of Human Unmyelinated Peripheral Axons 英文参考文献.doc

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GABA Increases Electrical Excitability in a Subset of Human Unmyelinated Peripheral Axons 英文参考文献

GABAIncreasesElectricalExcitabilityinaSubsetof HumanUnmyelinatedPeripheralAxons RichardW.Carr1*,RuthSittl1,JohannesFleckenstein2,PeterGrafe1 1InstituteofPhysiology,Ludwig-MaximiliansUniversity,Munich,Germany,2DepartmentofAnaesthesiology,Ludwig-MaximiliansUniversity,Munich,Germany Abstract Background:Aproportionofsmalldiameterprimarysensoryneuronesinnervatinghumanskinarechemosensitive.They respondinareceptordependentmannertochemicalmediatorsofinflammationaswellasnaturallyoccurringalgogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on humanperipheralunmyelinatedaxonshasnotbeenestablished. Methodology/PrincipalFindings:ElectricalstimulationwasusedtoassesstheeffectofGABAontheelectricalexcitabilityof unmyelinated axons in isolated fascicles of human sural nerve. GABA (0.1–100 mM) increased electrical excitability in a subset(ca.40%)ofC-fibresinhumansuralnervefasciclessuggestingthataxonalGABAsensitivityisselectivelyrestrictedto asub-populationofhumanunmyelinatedaxons.TheeffectsofGABAweremediatedbyGABA receptors,beingmimicked A bybathapplicationoftheGABA agonistmuscimol(0.1–30mM)whiletheGABABagonistbaclofen(10–30mM)waswithout A effect. Increases in excitability produced by GABA (10–30mM) were blocked by the GABAA antagonists gabazine (10– 20mM),bicuculline(10–20mM)andpicrotoxin(10–20mM). Conclusions/Significance: Functional GABAA receptors are present on a subset of unmyelinated primary afferents in humansandtheiractivationdepolarizestheseaxons,aneffectlikelyduetoanelevatedintra-axonalchlorideconcentration. GABAAreceptormodulationmaythereforeregulatesegmentalandperipheralcomponentsofnociception. Citation:CarrRW,SittlR,FleckensteinJ,GrafeP(2010)GABAIncreasesElectricalExcitabilityinaSubsetofHumanUnmyelinatedPeripheralAxons.PLoSONE5(1): e8780.doi:10.1371/journal.pone.0008780 Editor:F