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Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release

Szabó, Gergely G ; Lenkey, Nora ; Holderith, Noemi ; Andrási, Tibor ; Nusser, Zoltan ; Hájos, Norbert

The Journal of neuroscience, 2014-06, Vol.34 (23), p.7958-7963 [Periódico revisado por pares]

United States: Society for Neuroscience

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Título:
Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release
Autor: Szabó, Gergely G ; Lenkey, Nora ; Holderith, Noemi ; Andrási, Tibor ; Nusser, Zoltan ; Hájos, Norbert
Assuntos: Animals ; Animals, Newborn ; Brief Communications ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Cholecystokinin - genetics ; Cholecystokinin - pharmacology ; Female ; gamma-Aminobutyric Acid - metabolism ; Hippocampus - cytology ; In Vitro Techniques ; Inhibitory Postsynaptic Potentials - drug effects ; Inhibitory Postsynaptic Potentials - physiology ; Interneurons - drug effects ; Interneurons - physiology ; Luminescent Proteins - genetics ; Male ; Mice ; Mice, Transgenic ; omega-Conotoxin GVIA - pharmacology ; Piperidines - pharmacology ; Presynaptic Terminals - drug effects ; Presynaptic Terminals - metabolism ; Pyrazoles - pharmacology ; Receptor, Cannabinoid, CB1 - metabolism ; Synapses - drug effects ; Synapses - physiology
É parte de: The Journal of neuroscience, 2014-06, Vol.34 (23), p.7958-7963
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
G.G.S. and N.L. contributed equally to this work.
Z.N. and N. Hajos contributed equally to this work.
Author contributions: Z.N. and N. Hajos designed research; G.G.S., N.L., N. Holderith, and T.A. performed research; G.G.S., N.L., N. Holderith, and T.A. analyzed data; G.G.S., N.L., N. Holderith, Z.N., and N. Hajos wrote the paper.
Descrição: CB1 cannabinoid receptors (CB1) are located at axon terminals and effectively control synaptic communication and thereby circuit operation widespread in the CNS. Although it is partially uncovered how CB1 activation leads to the reduction of synaptic excitation, the mechanisms of the decrease of GABA release upon activation of these cannabinoid receptors remain elusive. To determine the mechanisms underlying the suppression of synaptic transmission by CB1 at GABAergic synapses, we recorded unitary IPSCs (uIPSCs) at cholecystokinin-expressing interneuron-pyramidal cell connections and imaged presynaptic [Ca(2+)] transients in mouse hippocampal slices. Our results reveal a power function with an exponent of 2.2 between the amplitude of uIPSCs and intrabouton [Ca(2+)]. Altering CB1 function by either increasing endocannabinoid production or removing its tonic activity allowed us to demonstrate that CB1 controls GABA release by inhibiting Ca(2+) entry into presynaptic axon terminals via N-type (Cav2.2) Ca(2+) channels. These results provide evidence for modulation of intrabouton Ca(2+) influx into GABAergic axon terminals by CB1, leading to the effective suppression of synaptic inhibition.
Editor: United States: Society for Neuroscience
Idioma: Inglês

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Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release

Szabó, Gergely G ; Lenkey, Nora ; Holderith, Noemi ; Andrási, Tibor ; Nusser, Zoltan ; Hájos, Norbert

United States: Society for Neuroscience

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