Distribution and functional expression of Kv4 family α subunits and associated KChIP β subunits in the bed nucleus of the stria terminalis

J Comp Neurol. 2014 Feb 15;522(3):609-25. doi: 10.1002/cne.23435.


Regulation of BNSTALG neuronal firing activity is tightly regulated by the opposing actions of the fast outward potassium current, IA , mediated by α subunits of the Kv4 family of ion channels, and the transient inward calcium current, IT . Together, these channels play a critical role in regulating the latency to action potential onset, duration, and frequency, as well as dendritic back-propagation and synaptic plasticity. Previously we have shown that Type I-III BNSTALG neurons express mRNA transcripts for each of the Kv4 α subunits. However, the biophysical properties of native IA channels are critically dependent on the formation of macromolecular complexes of Kv4 channels with a family of chaperone proteins, the potassium channel-interacting proteins (KChIP1-4). Here we used a multidisciplinary approach to investigate the expression and function of Kv4 channels and KChIPs in neurons of the rat BNSTALG . Using immunofluorescence we demonstrated the pattern of localization of Kv4.2, Kv4.3, and KChIP1-4 proteins in the BNSTALG . Moreover, our single-cell reverse-transcription polymerase chain reaction (scRT-PCR) studies revealed that mRNA transcripts for Kv4.2, Kv4.3, and all four KChIPs were differentially expressed in Type I-III BNSTALG neurons. Furthermore, immunoelectron microscopy revealed that Kv4.2 and Kv4.3 channels were primarily localized to the dendrites and spines of BNSTALG neurons, and are thus ideally situated to modulate synaptic transmission. Consistent with this observation, in vitro patch clamp recordings showed that reducing postsynaptic IA in these neurons lowered the threshold for long-term potentiation (LTP) induction. These results are discussed in relation to potential modulation of IA channels by chronic stress.

Keywords: LTP; electron microscopy; patch clamp; single cell RT-PCR; voltage-dependent potassium channel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Analysis of Variance
  • Animals
  • Biophysics
  • Electric Stimulation
  • In Vitro Techniques
  • Kv Channel-Interacting Proteins / genetics
  • Kv Channel-Interacting Proteins / metabolism*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Microscopy, Immunoelectron
  • Neurons / classification
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • RNA, Messenger
  • Rats
  • Rats, Sprague-Dawley
  • Septal Nuclei / anatomy & histology*
  • Septal Nuclei / metabolism*
  • Shal Potassium Channels / genetics
  • Shal Potassium Channels / metabolism*
  • Subcellular Fractions / metabolism
  • Subcellular Fractions / ultrastructure


  • Kv Channel-Interacting Proteins
  • Potassium Channel Blockers
  • RNA, Messenger
  • Shal Potassium Channels
  • 4-Aminopyridine