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

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.

Central CRF neurons are not created equal: phenotypic differences in CRF-containing neurons of the rat paraventricular hypothalamus and the bed nucleus of the stria terminalis

“…Although we did not observe burst firing in the current study, we have confirmed that the parvocellular PVN neurons, which expressed CRF, also co-expressed Cav 3.1 and Cav 3.2 subunits mediating the I T currents. Conversely, the Type III putative CRF neurons in the BNST do not exhibit low-threshold firing indicative of an I T current (Hammack et al, 2007), but do show significant I A currents (Rainnie et al, 2013). However, in the current study we have shown that the great majority of Type III, putative CRF neurons of the BNST ALG co-expressed Cav 3.3 subunit.…”

Chronic stress induces cell type-selective transcriptomic and electrophysiological changes in the bed nucleus of the stria terminalis

“…Whole-cell recordings were obtained as previously described (Rainnie, Hazra et al 2014). Neurons were patched using one of three different recording patch solutions depending on the experiment being done.…”

BmP02 Atypically Delays Kv4.2 Inactivation: Implication for a Unique Interaction between Scorpion Toxin and Potassium Channel

“…Kv4.2 and Kv4.3 are major mediators of I to or I A in nervous system and heart [3,4], and their blockage or dysfunction is associated with pathologies, including pain, epilepsy, atrial fibrillation and long QT syndrome [5,6,7,8]. However, our understanding on the gating mechanism and structural characteristics of Kv4 channels is much less advanced compared to the Kv1 channel family.…”