Distribution and Functional Expression of Kv4 Family α Subunits and Associated KChIP β Subunits in the Bed Nucleus of the Stria Terminalis

• Type of Material: Article
• Authors: Donald G. Rainnie, Emory University; Rimi Hazra, Emory University; Joanna Dabrowska, Emory University; Ji-Dong Guo, Emory University; Chen Chen Li, Emory University; Sarah Dewitt, Emory University; Chris E. Muly, Emory University
• Language: English
• Date: 2014-02-15
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Wiley Periodicals, Inc
• Final Published Version (URL): http://dx.doi.org/10.1002/cne.23435
• Title of Journal or Parent Work: Journal of Comparative Neurology
• Volume: 522
• Issue: 3
• Start Page: 609
• End Page: 625
• Grant/Funding Information: Grant sponsor: NIMH; Grant number: MH072908 (to D.G.R.); Grant sponsor: Merit Award from the Office of Research and Development, Department of Veterans Affairs (to E.C.M.); Grant sponsor: National Center for Research Resources; Grant number: P51RR169; Grant sponsor: NIH; Grant number: P51 OD011132; Grant sponsor: Office of Research Infrastructure Programs; Grant number: OD P51OD11107.
• Keywords: Neurosciences & Neurology; INTRINSIC EXCITABILITY; POTASSIUM CHANNELS; K+ CURRENT; Life Sciences & Biomedicine; single cell RT-PCR; MODULATION; LONG-TERM POTENTIATION; CURRENTS; MOUSE; DIFFERENTIAL EXPRESSION; CHANNEL-INTERACTING PROTEINS; NMDA RECEPTOR; patch clamp; LTP; Neurosciences; voltage-dependent potassium channel; Zoology; Science & Technology; electron microscopy
• Research Categories: Chemistry, Biochemistry; Biology, Animal Physiology; Biology, Neuroscience

Abstract

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. J. Comp. Neurol. 522:609-625, 2014. © 2013 Wiley Periodicals, Inc.