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

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.

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