Park YY, Johnston D, Gray R. Slowly inactivating component of Na ϩ current in peri-somatic region of hippocampal CA1 pyramidal neurons. J Neurophysiol 109: 1378 -1390, 2013. First published December 12, 2012 doi:10.1152/jn.00435.2012.-The properties of voltage-gated ion channels on the neuronal membrane shape electrical activity such as generation and backpropagation of action potentials, initiation of dendritic spikes, and integration of synaptic inputs. Subthreshold currents mediated by sodium channels are of interest because of their activation near rest, slow inactivation kinetics, and consequent effects on excitability. Modulation of these currents can also perturb physiological responses of a neuron that might underlie pathological states such as epilepsy. Using nucleated patches from the peri-somatic region of hippocampal CA1 neurons, we recorded a slowly inactivating component of the macroscopic Na ϩ current (which we have called I NaS ) that shared many biophysical properties with the persistent Na ϩ current, I NaP , but showed distinctively faster inactivating kinetics. Ramp voltage commands with a velocity of 400 mV/s were found to elicit this component of Na ϩ current reliably. I NaS also showed a more hyperpolarized I-V relationship and slower inactivation than those of the fast transient Na ϩ current (I NaT ) recorded in the same patches. The peak amplitude of I NaS was proportional to the peak amplitude of I NaT but was much smaller in amplitude. Hexanol, riluzole, and ranolazine, known Na ϩ channel blockers, were tested to compare their effects on both I NaS and I NaT . The peak conductance of I NaS was preferentially blocked by hexanol and riluzole, but the shift of half-inactivation voltage (V 1/2 ) was only observed in the presence of riluzole. Current-clamp measurements with hexanol suggested that I NaS was involved in generation of an action potential and in upregulation of neuronal excitability.

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