Molecular heterogeneity of the voltage-gated fast transient outward K+ current, IAf, in mammalian neurons

Sacha A. Malin, Jeanne M. Nerbonne

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Recently, we identified four kinetically distinct voltage-gated K+ currents, IAf, IAs, IK, and ISS, in rat superior cervical ganglion (SCG) neurons and demonstrated that IAf and IAs are differentially expressed in type I (IAf, IK, ISS), type II (IAf, IAs, IK, ISS), and type III (IK, ISS) SCG cells. In addition, we reported that IAf is eliminated in most (∼70%) SCG cells expressing Kv4.2W362F, a Kv4 subfamily-specific dominant negative. The molecular correlate(s) of the residual IAf, as well as that of IAs, IK, and ISS, however, are unknown. The experiments here were undertaken to explore the role of Kv1 α-subunits in the generation of voltage-gated K+ currents in SCG neurons. Using the Biolistics Gene Gun, cDNA constructs encoding a Kv1 subfamily-specific dominant negative, Kv1.5W461F, and enhanced green fluorescent protein (EGFP) were introduced into SCG neurons. Whole-cell recordings from EGFP-positive Kv1.5W461F-expressing cells revealed a selective decrease in the percentage of type I cells and an increase in type III cells, indicating that IAf is gated by Kv1 α-subunits in a subset of type I SCG neurons. IAf is eliminated in all SCG cells expressing both Kv1.5W461F and Kv4.2W362F. IAf τdecay values in Kv1.5W461F-expressing and Kv4.2W362F-expressing type I cells are significantly different, revealing that Kv1- and Kv4 α-subunits encode kinetically distinct IAf channels. Expression of Kv1.5W461F increases excitability by decreasing action potential current thresholds and converts phasic cells to adapting or tonic firing. Interestingly, the molecular heterogeneity of IAf channels has functional significance because Kv1 and Kv4-encoded IAf play distinct roles in the regulation of neuronal excitability.

Original languageEnglish
Pages (from-to)8004-8014
Number of pages11
JournalJournal of Neuroscience
Volume21
Issue number20
StatePublished - Oct 15 2001

Keywords

  • Gene gun
  • I
  • K channels
  • Kv1 α-subunits
  • Kv1.5W461F
  • Kv4 α-subunits
  • Neuronal excitability
  • Repetitive firing patterns
  • Transgenics

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