New solutions to the "solved" problem of how sodium channels control cortical neuronal excitability

60 years ago, Hodgkin and Huxley published their seminal papers which described the kinetics of voltage-gated ionic currents in the squid giant axon and used these measurements to produce the fundamental model of action potential generation.  Their findings have become the basis for our understanding of neuronal excitability and information processing and are central to computational models of neuronal function.  However, it turns out that the precise activation and inactivation characteristics of voltage-gated sodium channels in the CNS can vary widely, not only depending on the brain region, cell type and molecular subunit, but also as a function of the location of channels within the neuron and their relationship to the local membrane cytoskeleton.  These differences in current properties can have a profound functional impact.   I will discuss our data on transient and persistent sodium currents in the various compartments of the cortical pyramidal neuron, collected in brain slices using whole-cell current and on-cell single channel recordings and imaging of sodium-sensitive fluorescent dyes.