Phosphorylation‐dependent differences in the activation properties of distal and proximal dendritic Na+ channels in rat CA1 hippocampal neurons

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Abstract
At distal dendritic locations, the threshold for action potential generation is higher and the amplitude of back‐propagating spikes is decreased. To study whether these characteristics depend upon Na+ channels, their voltage‐dependent properties at proximal and distal dendritic locations were compared in CA1 hippocampal neurons. Distal Na+ channels activated at more hyperpolarized voltages than proximal (half‐activation voltages were −20.4 ± 2.4 mV vs.−12.0 ± 1.7 mV for distal and proximal patches, respectively, n= 16, P < 0.01), while inactivation curves were not significantly different. The resting membrane potential of distal regions also appeared to be slightly but consistently more hyperpolarized than their proximal counterpart. Staurosporine, a non‐selective protein kinase inhibitor, shifted the activation curves for both proximal and distal Na+ channels to the left so that they overlapped and also caused the resting potentials to be comparable. Staurosporine affected neither the inactivation kinetics of Na+ currents nor the reversal potential for Na+. These results suggest that the difference in the voltage dependence of activation of distal and proximal Na+ channels can be attributed to a different phosphorylation state at the two locations.