This is the readme for the models associated with the publication
Nayak TK, Sikdar SK (2007) Time-dependent molecular memory in single
voltage-gated sodium channel. J Membr Biol 219:19-36
Neuronal excitability is associated with firing of action potentials
and requires the opening of voltage gated sodium channels with
membrane depolarization. Sustained membrane depolarization, as seen in
pathophysiological conditions like Epilepsy, can have profound
implication on the biophysical properties of voltage gated ion
channels. Here we illustrate novel non-linear properties of voltage
gated Na+ channel induced by sustained membrane depolarization. In
cell-attached patch clamp recordings of rNav1.2 channels expressed in
CHO cells, we found complex non-linear changes in the molecular
kinetic properties, including channel dwell times and unitary
conductance of single Na+ channels that were dependent on the extent
of conditioning membrane depolarization. Hidden Markov Model (HMM)
suggested that a single kinetic model could not describe the single
sodium channel current with varying durations of conditioning
depolarization. A °»molecular memory°… phenomenon arises at longer
depolarization characterized by clusters of dwell time events and
strong autocorrelation in dwell times. Persistence of such molecular
memory was dependent on the duration of conditioning
depolarization. HMM modeling also suggested a possible explanation to
the memory phenomenon. It suggests that sustained depolarization
induces a °∆time-dependent molecular memory°« of previous activity in
the channel protein that determines the functional state of the
voltage gated Na+ channel, which in turn, can determine the
excitability of a neuron.
Usage: these models run in the "Yale HMM" software developed in the
laboratory of Fred Sigworth at Yale University.
The models have been named according to the nomenclature used in Table
1 as well as in the text in the manuscript.
These model files were supplied by Tapan Kumar Nayak.
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