Muscarinic modulation of high frequency oscillations in pedunculopontine neurons

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 ch...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Kezunovic, N., Hyde, J., Goitia, B., Bisagno, V., Urbano, F.J., Garcia-Rill, E.
Formato: JOUR
Materias:
5'-[β-thio] diphosphate trilithium salt
5'-[γ-thio] triphosphate trilithium salt
Calcium channels
Carbachol
G-proteins
Gamma oscillations
Muscarinic receptors
acetylcholine
atropine
calcium channel
carbachol
cholinergic receptor
guanine nucleotide binding protein
muscarinic M2 receptor
potassium channel
voltage gated sodium channel
animal cell
animal experiment
article
brain stem
calcium current
cell density
controlled study
dendrite
electroencephalogram
female
high frequency oscillation
male
membrane potential
nerve cell
nerve cell membrane potential
nerve cell membrane steady potential
neuromodulation
nonhuman
patch clamp technique
pedunculopontine tegmental nucleus
protein function
rat
substantia nigra pars compacta
voltage clamp technique
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_16642295_v4NOV_n_p_Kezunovic
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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. © 2013 Kezunovic, Hyde, Goitia, Bisagno, Urbano and Garcia-Rill.

Ejemplares similares