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J Neurophysiol (January 10, 2007). doi:10.1152/jn.00933.2006
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Submitted on September 1, 2006
Accepted on January 9, 2007

Functional roles of Kv1 channels in neocortical pyramidal neurons

Dongxu Guan1, Jonathan cf Lee1, Matthew h Higgs2, William J. Spain2, and Robert C Foehring1*

1 Anatomy and Neurobiology, University of Tennessee, Memphis, Tennessee, United States
2 Neurology, University of Washington, Seattle, Washington, United States

* To whom correspondence should be addressed. E-mail: rfoehrin{at}utmem.edu.

Pyramidal neurons from layers II/III of somatosensory and motor cortex express multiple Kv1 {alpha}-subunits and a current sensitive to block by {alpha}-dendrotoxin ({alpha}-DTX: Guan et al. 2006). 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. {alpha}-DTX caused a significant negative shift in voltage threshold for action potentials (APs) and reduced rheobase. Correspondingly, a ramp voltage protocol revealed that the {alpha}-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 {alpha}-DTX, despite an initially broader AP in {alpha}-DTX. AP voltage threshold increased similarly during a train of spikes under control conditions and in the presence of {alpha}-DTX. {alpha}-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 {alpha}-DTX-sensitive current peaked late during the AP repolarization phase. Application of {alpha}-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 {alpha}-DTX was highest during the interval between two APWs, reflecting slow deactivation kinetics at -50 mV. Finally, {alpha}-DTX did not alter the selectivity of pyramidal neurons for DC vs. time varying stimuli.|




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