Functional roles of Kv1 channels in neocortical pyramidal neurons.
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). 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 versus time-varying stimuli.
Guan
D
D
Department of Anatomy and Neurobiology, University of Tennessee, 855 Monroe Avenue, Memphis, TN 38163, USA.
Lee
J C F
JC
Higgs
M H
MH
Spain
W J
WJ
Foehring
R C
RC
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D019579:Neocortex / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051381:Rats; D051637:Shaker Superfamily of Potassium Channels / Q000502:physiology*
D004546:Elapid Venoms; D026902:Potassium Channel Blockers; D051637:Shaker Superfamily of Potassium Channels; C020273:dendrotoxin