Linked Life Data

18680743

Source:http://linkedlifedata.com/resource/pubmed/id/18680743

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-9-16
pubmed:abstractText
Parkinson's disease (PD) is characterized by loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). It is widely believed that replacing lost SNc DA neurons is a key to longer-term effective treatment of PD motor symptoms, but generating new SNc DA neurons in PD patients has proven difficult. Following loss of tyrosine hydroxylase-positive (TH+) SNc neurons in the rodent 6-hydroxy-DA (6-OHDA) model of PD, the number of TH+ neurons partially recovers and there is evidence this occurs via phenotype "shift" from TH- to TH+ cells. Understanding how this putative phenotype shift occurs may help increase SNc DAergic neurons in PD patients. In this study we characterize the electrophysiology of SNc TH- and TH+ cells during recovery from 6-OHDA in mice. Three distinct phenotypes were observed: (1) TH- were fast discharging with a short duration action potential (AP), short afterhyperpolarization (AHP) and no small conductance Ca(2+)-activated K(+) (SK) current; (2) TH+ were slow discharging with a long AP, long AHP and prominent SK current; and (3) cells with features "intermediate" between these TH- and TH+ phenotypes. The same 3 phenotypes were present also in the normal and D2 DA receptor knock-out SNc suggesting they are more closely related to the biology of TH expression than recovery from 6-OHDA. Acute inhibition of SK channel function shifted the electrophysiological phenotype of TH+ neurons toward TH- and chronic (2 weeks) inhibition of SK channel function in normal mice shifted the neurochemical phenotype of SNc from TH+ to TH- (i.e. decreased TH+ and increased TH- cell numbers). Importantly, chronic facilitation of SK channel function shifted the neurochemical phenotype of SNc from TH- to TH+ (i.e. increased TH+ and decreased TH- cell numbers). We conclude that SK channel function bidirectionally regulates the DA phenotype of SNc cells and facilitation of SK channels may be a novel way to increase the number of SNc DAergic neurons in PD patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1090-2430
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
213
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
419-30
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
SK channel function regulates the dopamine phenotype of neurons in the substantia nigra pars compacta.
pubmed:affiliation
Howard Florey Institute, The University of Melbourne, Parkville, Victoria, Australia.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't