Electrical remodeling of preoptic GABAergic neurons involves the Kv1.5 subunit.

Iustin V Tabarean,Stefan Strack

doi:10.1371/journal.pone.0096643

Abstract

The electrogenic machinery of an excitable cell can adapt in response to changes in input, genetic deficit or in pathological conditions, however the underlying molecular mechanisms are not understood. In cases of genetic deletion it is commonly observed that a channel subunit from the same family replaces the missing one. We have previously reported that Kv4.2−/− preoptic GABAergic neurons display identical firing characteristics to those of wild-type neurons despite having reduced A-type currents, and that, surprisingly, they present a robust upregulation of a delayed rectifier current, the nature of which is unknown. Here, using pharmacology, qPCR and Western blots we report that, although the wild-type neurons express several Kv subunits, the upregulated current is conducted by the Kv1.5 subunit exclusively. Thus, this study reveals the molecular nature of a novel mechanism of electrical remodeling in central neurons.

Highlights

Excitable cells can remodel the complement of voltage-gated channel they express in response to changes in physiological input or in pathological conditions [1,2,3,4]
This data clarifies the molecular nature of the upregulated in the delayed rectifier current (IDR) in preoptic GABAergic neurons of Kv4.22/2;GAD65-GFP mice
QPCR and Western blots we identify Kv1.5 as the subunit responsible for the bulk of the upregulated IDR component

Summary

Introduction

Excitable cells can remodel the complement of voltage-gated channel they express in response to changes in physiological input or in pathological conditions [1,2,3,4]. Kv4.22/2 GABAergic preoptic neurons present identical firing properties with w-t neurons they have reduced A-type currents (in spite of compensatory upregulation of the Kv4.1 subunit) [7]. These neurons present a robust upregulation in the delayed rectifier current (IDR) [7]. In order to gain further insights in the mechanisms of electrical remodeling in preoptic neurons, in this study we have determined the molecular nature and the electrophysiological properties of the increased IDR of Kv4.22/2 GABAergic preoptic neurons to test the hypotheses that the upregulation involves a specific Kv channel subunit and that it is responsible for the conserved firing characteristics of Kv4.22/2 neurons

Materials and Methods

Results

Findings

Discussion