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HERG K+ channels spike-frequency adaptation (Chiesa et al 1997)
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This is the readme.txt for the model associated with the paper Chiesa N, Rosati B, Arcangeli A, Olivotto M, Wanke E. A novel role for HERG K+ channels: spike-frequency adaptation. J Physiol 1997;501:313-318 Abstract: 1. The regular firing of a Hodgkin-Huxley neurone endowed with fast Na+ and delayed K+ channels can be converted into adapting firing by appending HERG (human eag-related gene) channels. 2. The computer model predictions were verified by studying the firing properties of F-11 DRG neurone x neuroblastoma hybrid cells induced to differentiate by long- term exposure to retinoic acid. These cells, which express HERG currents (IHERG), show clear spike-frequency adaptation of their firing when current clamped with long depolarizations. 3. In agreement with the prediction, the selective blocking of IHERG by class III antiarrhythmic drugs always led to the disappearance of the spike- frequency adaptation, and the conversion of adapting firing to regular firing. 4. It is proposed that, in addition to their role in the repolarization of the heart action potential, HERG channels may sustain a process of spike-frequency adaptation, and hence contribute to the control of burst duration in a way that is similar to that of the K+ currents, IAHP, IC and IM. In addition to the known cardiac arrhythmia syndrome (LQT2), genetic mutations or an altered HERG expression could lead to continuous hyperexcitable states sustained by the inability of nerve or endocrine cells to accommodate to repetitive stimuli. This might help in clarifying the pathogenesis of still undefined idiopathic familial epilepsies. --- To run the models: XPP: start with the command xpp ode\kir_sim.ode Mouse click on Initialconds, and then (G)o. This makes a trace similar to fig 1E of the paper. Regarding xpp program, please contact with Bard Ermentrout's website http://www.pitt.edu/~phase/ describes how to get and use xpp (Bard wrote xpp). These model files were submitted by: Dr. Sheng-Nan Wu Dept Physiol Natl Cheng Kung U Med Coll Tainan 70101, Taiwan snwu@mail.ncku.edu.tw
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