Linked Life Data

20974975

Source:http://linkedlifedata.com/resource/pubmed/id/20974975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2010-12-1
pubmed:abstractText
Fast axonal conduction of action potentials in mammals relies on myelin insulation. Demyelination can cause slowed, blocked, desynchronized, or paradoxically excessive spiking that underlies the symptoms observed in demyelination diseases. The diversity and timing of such symptoms are poorly understood, often intermittent, and uncorrelated with disease progress. We modeled the effects of demyelination (and secondary remodeling) on intrinsic axonal excitability using Hodgkin-Huxley and reduced Morris-Lecar models. Simulations and analysis suggested a simple explanation for the breadth of symptoms and revealed that the ratio of sodium to leak conductance, g(Na)/g(L), acted as a four-way switch controlling excitability patterns that included spike failure, single spike transmission, afterdischarge, and spontaneous spiking. Failure occurred when this ratio fell below a threshold value. Afterdischarge occurred at g(Na)/g(L) just below the threshold for spontaneous spiking and required a slow inward current that allowed for two stable attractor states, one corresponding to quiescence and the other to repetitive spiking. A neuron prone to afterdischarge could function normally unless it was switched to its "pathological" attractor state; thus, although the underlying pathology may develop slowly by continuous changes in membrane conductances, a discontinuous change in axonal excitability can occur and lead to paroxysmal symptoms. We conclude that tonic and paroxysmal positive symptoms as well as negative symptoms may be a consequence of varying degrees of imbalance between g(Na) and g(L) after demyelination. The KCNK family of g(L) potassium channels may be an important target for new drugs to treat the symptoms of demyelination.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
30
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20602-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Imbalance of ionic conductances contributes to diverse symptoms of demyelination.
pubmed:affiliation
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. coggan@salk.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't