Dataset Information

Honeybee locomotion is impaired by Am-Ca_V3 low voltage-activated Ca²⁺ channel antagonist.

ABSTRACT: Voltage-gated Ca²⁺ channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca²⁺ channel genes, grouped in 3 families (Ca_V1, Ca_V2 and Ca_V3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial role, they may represent a collateral target for neurotoxic insecticides. We have isolated the 3 genes coding for the 3 Ca²⁺ channels expressed in Apis mellifera. This work provides the first detailed characterization of the honeybee T-type Ca_V3 Ca²⁺ channel and demonstrates the low toxicity of inhibiting this channel. Comparing Ca²⁺ currents recorded in bee neurons and myocytes with Ca²⁺ currents recorded in Xenopus oocytes expressing the honeybee Ca_V3 gene suggests native expression in bee muscle cells only. High-voltage activated Ca²⁺ channels could be recorded in the somata of different cultured bee neurons. These functional data were confirmed by in situ hybridization, immunolocalization and in vivo analysis of the effects of a Ca_V3 inhibitor. The biophysical and pharmacological characterization and the tissue distribution of Ca_V3 suggest a role in honeybee muscle function.

SUBMITTER: Rousset M

PROVIDER: S-EPMC5286435 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Honeybee locomotion is impaired by Am-CaV3 low voltage-activated Ca2+ channel antagonist.

Rousset M M Collet C C Cens T T Bastin F F Raymond V V Massou I I Menard C C Thibaud J-B JB Charreton M M Vignes M M Chahine M M Sandoz J C JC Charnet P P

Scientific reports 20170201

Voltage-gated Ca2+ channels are key transducers of cellular excitability and participate in several crucial physiological responses. In vertebrates, 10 Ca2+ channel genes, grouped in 3 families (CaV1, CaV2 and CaV3), have been described and characterized. Insects possess only one member of each family. These genes have been isolated in a limited number of species and very few have been characterized although, in addition to their crucial rol ...[more]

PMID: 28145504

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Project description:At chemical synapses, voltage-activated calcium channels (VACCs) mediate Ca2+ influx to trigger action potential-evoked neurotransmitter release. However, the mechanisms by which Ca2+ regulates spontaneous transmission have not been fully determined. We have shown that VACCs are a major trigger of spontaneous release at neocortical inhibitory synapses but not at excitatory synapses, suggesting fundamental differences in spontaneous neurotransmission at GABAergic and glutamatergic synapses. Recently, VACC blockers were reported to reduce spontaneous release of glutamate and it was proposed that there was conservation of underlying mechanisms of neurotransmission at excitatory and inhibitory synapses. Furthermore, it was hypothesized that the different effects on excitatory and inhibitory synapses may have resulted from off-target actions of Cd2+, a nonselective VACC blocker, or other variations in experimental conditions. Here we report that in mouse neocortical neurons, selective and nonselective VACC blockers inhibit spontaneous release at inhibitory but not at excitatory terminals, and that this pattern is observed in culture and slice preparations as well as in synapses from acute slices of the auditory brainstem. The voltage dependence of Cd2+ block of VACCs accounts for the apparent lower potency of Cd2+ on spontaneous release of GABA than on VACC current amplitudes. Our findings indicate fundamental differences in the regulation of spontaneous release at inhibitory and excitatory synapses by stochastic VACC activity that extend beyond the cortex to the brainstem.SIGNIFICANCE STATEMENT Presynaptic Ca2+ entry via voltage-activated calcium channels (VACCs) is the major trigger of action potential-evoked synaptic release. However, the role of VACCs in the regulation of spontaneous neurotransmitter release (in the absence of a synchronizing action potential) remains controversial. We show that spontaneous release is affected differently by VACCs at excitatory and inhibitory synapses. At inhibitory synapses, stochastic openings of VACCs trigger the majority of spontaneous release, whereas they do not affect spontaneous release at excitatory synapses. We find this pattern to be wide ranging, holding for large and small synapses in the neocortex and brainstem. These findings indicate fundamental differences of the Ca2+ dependence of spontaneous release at excitatory and inhibitory synapses and heterogeneity of the mechanisms of release across the CNS.

Dataset Information

Honeybee locomotion is impaired by Am-Ca_V3 low voltage-activated Ca²⁺ channel antagonist.

Publications

Honeybee locomotion is impaired by Am-Ca<sub>V</sub>3 low voltage-activated Ca<sup>2+</sup> channel antagonist.

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