Markov models of SCN1A (NaV1.1) applied to abnormal gating and epilepsy (Clancy and Kass 2004)

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Accession:87278
"Recently, some forms of idiopathic epilepsy have been causally related to genetic mutations in neuronal ion channels. To understand disease mechanisms, it is crucial to understand how a gene defect can disrupt channel gating, which in turn can affect complex cellular dynamic processes. We develop a theoretical Markovian model of the neuronal Na+ channel NaV1.1 to explore and explain gating mechanisms underlying cellular excitability and physiological and pathophysiological mechanisms of abnormal neuronal excitability in the context of epilepsy. ..."
Reference:
1 . Clancy CE, Kass RS (2004) Theoretical investigation of the neuronal Na+ channel SCN1A: abnormal gating and epilepsy. Biophys J 86:2606-14 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): I Na,t;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.1 SCN1A;
Transmitter(s):
Simulation Environment: C or C++ program;
Model Concept(s): Ion Channel Kinetics; Epilepsy;
Implementer(s): Clancy, Colleen E [ceclancy at ucdavis.edu];
Search NeuronDB for information about:  I Na,t;
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clancykass04
readme.txt
SCN1A_global_function.h
WT_SCN1A_function.cc
                            
This is the readme for the model associated with the paper:

Clancy CE, Kass RS (2004) Theoretical investigation of the neuronal
Na+ channel SCN1A: abnormal gating and epilepsy. Biophys J 86:2606-14

Abstract:
Epilepsy is a paroxysmal neurological disorder resulting from abnormal
cellular excitability and is a common cause of disability. Recently,
some forms of idiopathic epilepsy have been causally related to
genetic mutations in neuronal ion channels. To understand disease
mechanisms, it is crucial to understand how a gene defect can disrupt
channel gating, which in turn can affect complex cellular dynamic
processes. We develop a theoretical Markovian model of the neuronal
Na+ channel NaV1.1 to explore and explain gating mechanisms underlying
cellular excitability and physiological and pathophysiological
mechanisms of abnormal neuronal excitability in the context of
epilepsy. Genetic epilepsy has been shown to result from both
mutations that give rise to a gain of channel function and from those
that reduce the Na+ current. These data may suggest that abnormal
excitation can result from both hyperexcitability and
hypoexcitability, the mechanisms of which are presumably distinct, and
as yet elusive. Revelation of the molecular origins will allow for
translation into targeted pharmacological interventions that must be
developed to treat syndromes resulting from divergent mechanisms. This
work represents a first step in developing a comprehensive theoretical
model to investigate the molecular mechanisms underlying runaway
excitation that cause epilepsy.

We hope to provide soon usage instructions for this C++ function which was
originally implemented on a Apple Macintosh dual 800MhZ G4 with Apple
Developer Tools.




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