Functional Roles of Kv1 Channels in Neocortical Pyramidal Neurons

Abstract

Pyramidal neurons from layers II/III of somatosensory and motor cortex express multiple Kv1 α-subunits and a current sensitive to block by α-dendrotoxin (α-DTX). We examined functional roles of native Kv1 channels in these cells using current-clamp recordings in brain slices and current- and voltage-clamp recordings in dissociated cells. α-DTX caused a significant negative shift in voltage threshold for action potentials (APs) and reduced rheobase. Correspondingly, a ramp-voltage protocol revealed that the α-DTX–sensitive current activated at subthreshold voltages. AP width at threshold increased with successive APs during repetitive firing. The steady-state threshold width for a given firing rate was similar in control and α-DTX, despite an initially broader AP in α-DTX. AP voltage threshold increased similarly during a train of spikes under control conditions and in the presence of α-DTX. α-DTX had no effect on input resistance or resting membrane potential and modest effects on the amplitude or width of a single AP. Accordingly, experiments using AP waveforms (APWs) as voltage protocols revealed that α-DTX–sensitive current peaked late during the AP repolarization phase. Application of α-DTX increased the rate of firing to intracellular current injection and increased gain (multiplicative effects), but did not alter spike-frequency adaptation. Consistent with these findings, voltage-clamp experiments revealed that the proportion of outward current sensitive to α-DTX was highest during the interval between two APWs, reflecting slow deactivation kinetics at −50 mV. Finally, α-DTX did not alter the selectivity of pyramidal neurons for DC versus time-varying stimuli.