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Artículo

Muscarinic modulation of high frequency oscillations in pedunculopontine neurons

Kezunovic, Nebojsa; Hyde, James; Goitia, BelénIcon ; Bisagno, VeronicaIcon ; Urbano Suarez, Francisco JoseIcon ; Garcia Rill, Edgar
Fecha de publicación: 11/2013
Editorial: Frontiers Research Foundation
Revista: Frontiers in Neurology
ISSN: 1664-2295
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Biofísica

Resumen

We previously reported that persistent application of the non-specific cholinergic agonist carbachol (CAR) increased the frequency of calcium channel-mediated oscillatory activity in pedunculopontine nucleus (PPN) neurons, which we identified as dependent on voltage-gated, high-threshold P/Q-type channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in oscillatory frequency in PPN neurons. We found, using depolarizing ramps, that patch clamped 9-12 day old rat PPN neurons (n = 189) reached their peak oscillatory activity around -20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors, an effect blocked by atropine. However, persistent (long duration) application of CAR significantly increased the frequency of oscillatory activity in PPN neurons through M2 receptors [40 ± 1 Hz (with CAR) vs. 23 ± 1 Hz (without CAR); p < 0.001]. We then tested the effects of the G-protein antagonist guanosine 5'-[β-thio] diphosphate trilithium salt (GDP-β-S), and the G-protein agonist 5'-[γ-thio] triphosphate trilithium salt (GTP-γ-S). We found, using a three-step protocol in voltage-clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was linked to a voltage-dependent G-protein mechanism. In summary, these results suggest that persistent cholinergic input creates a permissive activation state in the PPN that allows high frequency P/Q-type calcium channel-mediated gamma oscillations to occur.
Palabras clave: 5'-[Β-THIO] DIPHOSPHATE TRILITHIUM SALT , 5'-[Γ-THIO] TRIPHOSPHATE TRILITHIUM SALT , CALCIUM CHANNELS , CARBACHOL , G-PROTEINS , GAMMA OSCILLATIONS , MUSCARINIC RECEPTORS
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/85190
DOI: http://dx.doi.org/10.3389/fneur.2013.00176
URL: https://www.frontiersin.org/articles/10.3389/fneur.2013.00176/full
Colecciones
Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos(ININFA)
Articulos de INST.DE INVEST.FARMACOLOGICAS (I)
Citación
Kezunovic, Nebojsa; Hyde, James; Goitia, Belén; Bisagno, Veronica; Urbano Suarez, Francisco Jose; et al.; Muscarinic modulation of high frequency oscillations in pedunculopontine neurons; Frontiers Research Foundation; Frontiers in Neurology; 4; NOV; 11-2013; 1-13
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