Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons - Archive ouverte HAL
Article Dans Une Revue eNeuro Année : 2021

Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons

Alexis Haddjeri-Hopkins
  • Fonction : Auteur
Mónica Tapia
Jorge Ramirez-Franco
Fabien Tell
Béatrice Marqueze-Pouey
  • Fonction : Auteur
Jean-Marc Goaillard

Résumé

Substantia nigra pars compacta (SNc) dopaminergic (DA) neurons display a peculiar electrical phenotype characterized in vitro by a spontaneous tonic regular activity (pacemaking activity), a broad action potential (AP) and a biphasic postinhibitory response. The transient A-type current (I A) is known to play a crucial role in this electrical phenotype, and so far, this current was considered to be carried exclusively by Kv4.3 potassium channels. Using Kv4.3À/À transgenic mice, we demonstrate that the constitutive loss of this channel is associated with increased exploratory behavior and impaired motor learning at the behavioral level. Consistently, it is also associated with a lack of compensatory changes in other ion currents at the cellular level. Using antigen retrieval (AR) immunohistochemistry, we then demonstrate that Kv4.2 potassium channels are also expressed in SNc DA neurons, although their contribution to I A appears significant only in a minority of neurons (;5-10%). Using correlative analysis on recorded electrophysiological parameters and multicompartment modeling, we then demonstrate that, rather than its conductance level, I A gating kinetics (inactivation time constant) appear as the main biophysical property defining postinhibitory rebound delay and pacemaking frequency. Moreover, we show that the hyperpolarization-activated current (I H) has an opposing and complementary influence on the same firing features.
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Dates et versions

hal-03414818 , version 1 (04-11-2021)

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Alexis Haddjeri-Hopkins, Mónica Tapia, Jorge Ramirez-Franco, Fabien Tell, Béatrice Marqueze-Pouey, et al.. Refining the Identity and Role of Kv4 Channels in Mouse Substantia Nigra Dopaminergic Neurons. eNeuro, 2021, 8, pp.ENEURO.0207 - 21.2021. ⟨10.1523/eneuro.0207-21.2021⟩. ⟨hal-03414818⟩
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