Ion Channel Gating by Molecular Components
As an ongoing project, the likely kinetic structure of gating, as determined for molecular subunits of the sodium and potassium ion channels in retinal ganglion cells, is applied to the corresponding channels of the squid giant axon, so as to recast the Hodgkin-Huxley model in terms of those kinetics. Remarkably, because of their pre-molecular era, Hodgkin and Huxley actually chose a kinetic structure that is easily applicable to the now known channel-molecular subunit structure; the primary change required is in the coupled nature of the Na-inactivation gating (the only other change is in the number 3 to 4 for the number of the Na-channel alpha subunits). Preliminary results show that a major puzzle of the Hodgkin-Huxley model - namely the model's oscillatory character, which differs fundamentally from squid axon behavior - is resolved by the new kinetics, which behaves like the squid axon due to its slow recovery from Na-inactivation after an action potential (this slow recovery from inactivation has also been documented by other investigators in other contexts). The project explores the new kinetics further, and is intended to determine the detailed gating-rate constants to match the raw voltage-clamp data used by Hodgkin and Huxley to fit thei model.
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