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Abstract

We transfected cultured hippocampal neurons with the cDNA of the voltage-gated K+ channel Kv1.3 to investigate the mechanisms by which a specific ion channel influences excitability. In transfected neurons under voltage clamp we observed an additional outward current that was blocked selectively by margatoxin. Under current-clamp conditions, Kv1.3-expressing neurons fired tonically over a wide range of stimulation intensity. In non-transfected neurons, or in Kv1.3- expressing cells blocked with margatoxin, only a few action potentials were elicited before a stationary depolarized state was reached. We attribute the specific effect of Kv1.3 to its particularly slow deactivation near the resting potential. A computational model showed that a continuous outwards current arises in Kv1.3-expressing neurons during the interspike intervals. It expands the dynamic range so that these neurons still fire tonically at stimulus current intensities at which non-transfected cells have already been driven into a stationary depolarized state.