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The Journal of Neuroscience, January 11, 2006, 26(2):671-684; doi:10.1523/JNEUROSCI.2283-05.2006
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Cellular/Molecular
Sodium Currents Activate without a Hodgkin and Huxley-Type Delay in Central Mammalian Neurons
Gytis Baranauskas1 and
Marco Martina2,3
1Psychiatric Institute, University of Illinois at Chicago, Chicago, Illinois 60612 and 2Department of Physiology, Feinberg School of Medicine, and 3Institute for Neuroscience, Northwestern University, Chicago, Illinois 60611
Hodgkin and Huxley established that sodium currents in the squid giant axons activate after a delay, which is explained by the model of a channel with three identical independent gates that all have to open before the channel can pass current (the HH model). It is assumed that this model can adequately describe the sodium current activation time course in all mammalian central neurons, although there is no experimental evidence to support such a conjecture. We performed high temporal resolution studies of sodium currents gating in three types of central neurons. The results show that, within the tested voltage range from -55 to -35 mV, in all of these neurons, the activation time course of the current could be fit, after a brief delay, with a monoexponential function. The duration of delay from the start of the voltage command to the start of the extrapolated monoexponential fit was much smaller than predicted by the HH model. For example, in prefrontal cortex pyramidal neurons, at -46 mV and 12°C, the observed average delay was 140 µs versus the 740 µs predicted by the two-gate HH model and the 1180 µs predicted by the three-gate HH model. These results can be explained by a model with two closed states and one open state. In this model, the transition between two closed states is approximately five times faster than the transition between the second closed state and the open state. This model captures all major properties of the sodium current activation. In addition, the proposed model reproduces the observed action potential shape more accurately than the traditional HH model.
Key words: dentate gyrus; granule cell; pyramidal cell; hippocampus; prefrontal cortex; sodium channel; CA1; action potential; activation; kinetics
Received June 4, 2005;
revised November 28, 2005;
accepted November 29, 2005.
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