Histamine H 3 Receptor Activation Modulates Glutamate Release in the Corticostriatal Synapse by Acting at Ca V 2.1 (P/Q-
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ORIGINAL RESEARCH
Histamine H3 Receptor Activation Modulates Glutamate Release in the Corticostriatal Synapse by Acting at CaV2.1 (P/Q‑Type) Calcium Channels and GIRK ( KIR3) Potassium Channels Héctor Vázquez‑Vázquez1 · Carolina Gonzalez‑Sandoval1 · Ana V. Vega2 · José‑Antonio Arias‑Montaño3 · Jaime Barral1 Received: 22 July 2020 / Accepted: 6 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The striatum is innervated by histaminergic fibers and expresses a high density of histamine H3 receptors (H3Rs), present on medium spiny neurons (MSNs) and corticostriatal afferents. In this study, in sagittal slices from the rat dorsal striatum, excitatory postsynaptic potentials (EPSPs) were recorded in MSNs after electrical stimulation of corticostriatal axons. The effect of H3R activation and blockers of calcium and potassium channels was evaluated with the paired-pulse facilitation protocol. In the presence of the H 3R antagonist/inverse agonist clobenpropit (1 μM), the H 3R agonist immepip (1 μM) had no effect on the paired-pulse ratio (PPR), but in the absence of clobenpropit, immepip induced a significant increase in PPR, accompanied by a reduction in EPSP amplitude, suggesting presynaptic inhibition. The blockade of CaV2.1 (P/Q-type) channels with ω-agatoxin TK (400 nM) increased PPR and prevented the effect of immepip. The C aV2.2 (N-type) channel blocker ω-conotoxin GVIA (1 μM) also increased PPR, but did not occlude the immepip action. Functional K IR3 channels are present in corticostriatal terminals, and in experiments in which immepip increased PPR, the K IR3 blocker tertiapin-Q (30 nM) prevented the effect of the H3R agonist. These results indicate that the presynaptic modulation by H 3Rs of corticostriatal synapses involves the inhibition of Cav2.1 calcium channels and the activation of KIR3 potassium channels. Keywords Presynaptic modulation · H3 receptors · KIR3 potassium channels · CaV2 calcium channels · Corticostriatal synapse Abbreviations D1-MSN D1 receptor-expressing medium spiny neuron D2-MSN D2 receptor-expressing medium spiny neuron EPSP Excitatory postsynaptic potential
GIRK G protein-activated inwardly rectifying potassium channel H3R Histamine H3 receptor; MSN Medium spiny neuron PPR Paired-pulse ratio
* Jaime Barral [email protected]
Introduction
1
Departamento de Neurociencias, UIICSE, Facultad de Estudios Superiores Iztacala, UNAM, Av. de los Barrios 1, Los Reyes Iztacala, Apartado Postal 314, 54090 Tlalnepantla, Estado de México, Mexico
2
Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, UNAM, Av. de los Barrios 1, Los Reyes Iztacala, Apartado Postal 314, 54090 Tlalnepantla, Estado de México, Mexico
3
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación Y de Estudios Avanzados (Cinvestav) del IPN, Av. IPN 2508, 07360 Zacatenco, Ciudad de México, Mexico
The striatum is the main input structure of the basal ganglia, a group of neuronal nuclei with a cri
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