Calcium Channel Diversity at the Vertebrate Neuromuscular Junction

Homeostatic signaling stabilizes synaptic transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human. It is believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been made identifying mechanisms underlying the homeostatic potentiation of neurotransmitter release. However, very little is understood mechanistically about the opposing process, homeostatic depression, and how bi-directional plasticity is achieved. Here, we show that homeostatic potentiation and depression can be simultaneously induced, demonstrating true bi-directional plasticity. Next, we show that mutations that block homeostatic potentiation do not alter homeostatic depression, demonstrating that these are genetically separable processes. Finally, we show that homeostatic depression is achieved by decreased presynaptic calcium channel abundance and calcium influx, changes that are independent of the presynaptic action potential waveform. Thus, we identify a novel mechanism of homeostatic synaptic plasticity and propose a model that can account for the observed bi-directional, homeostatic control of presynaptic neurotransmitter release.

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Genetic and Developmental Characterization of Dmca1D, a Calcium Channel α1 Subunit Gene in Drosophila melanogaster

Genetics ◽

10.1093/genetics/148.3.1159 ◽

1998 ◽

Vol 148 (3) ◽

pp. 1159-1169

Author(s):

Daniel F Eberl ◽

Dejian Ren ◽

Guoping Feng ◽

Lori J Lorenz ◽

David Van Vactor ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Calcium Channel ◽

Functional Significance ◽

Transmembrane Domain ◽

Vital Role ◽

Subunit Gene ◽

Channel Diversity ◽

Domain I ◽

Α1 Subunit

Abstract To begin unraveling the functional significance of calcium channel diversity, we identified mutations in Dmca1D, a Drosophila calcium channel α1 subunit cDNA that we recently cloned. These mutations constitute the l(2)35Fa lethal locus, which we rename Dmca1D. A severe allele, Dmca1DX10, truncates the channel after the IV-S4 transmembrane domain. These mutants die as late embryos because they lack vigorous hatching movements. In the weaker allele, Dmca1DAR66, a cysteine in transmembrane domain I-S1 is changed to tyrosine. Dmca1DAR66 embryos hatch but pharate adults have difficulty eclosing. Those that do eclose have difficulty in fluid-filling of the wings. These studies show that this member of the calcium channel α1 subunit gene family plays a nonredundant, vital role in larvae and adults.

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Calcium Channel Diversity

Encyclopedia of Life Sciences ◽

10.1002/9780470015902.a0000087.pub3 ◽

2019 ◽

pp. 1-9

Author(s):

Annette C Dolphin

Keyword(s):

Calcium Channel ◽

Channel Diversity

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Pharmacologically and Functionally Distinct Calcium Currents of Stomatogastric Neurons

Journal of Neurophysiology ◽

10.1152/jn.1998.79.4.2070 ◽

1998 ◽

Vol 79 (4) ◽

pp. 2070-2081 ◽

Cited By ~ 10

Author(s):

Laura M. Hurley ◽

Katherine Graubard

Keyword(s):

Neuromuscular Junction ◽

Calcium Channel ◽

Calcium Current ◽

Calcium Influx ◽

Outward Current ◽

Calcium Currents ◽

High Threshold ◽

Channel Blockers ◽

Postsynaptic Potentials ◽

Different Types

Hurley, Laura M. and Katherine Graubard. Pharmacologically and functionally distinct calcium currents of stomatogastric neurons. J. Neurophysiol. 79: 2070–2081, 1998. Previous studies have suggested the presence of different types of calcium channels in different regions of stomatogastric neurons. We sought to pharmacologically separate these calcium channel types. We used two different preparations from different regions of stomatogastric neurons to screen a range of selective calcium channel blockers. The two preparations were isolated cell bodies in culture, in which calcium current was measured directly, and isolated neuromuscular junction, in which synaptic transmission was the indirect assay for presynaptic calcium influx. The selective blockers were two different dihydropyridines, ω-Agatoxin IVA, and ω-Conotoxin GVIA. Cultured cell bodies possessed both high-threshold calcium current and calcium-activated outward current, similar to intact neurons. The calcium current had transient and maintained components, but both components had the same voltage dependence of activation and inactivation. Dihydropyridines at ≥10 μM blocked both high-threshold calcium current and calcium-activated outward current. Nanomolar doses of ω-Agatoxin IVA did not block calcium current, but micromolar doses did. ω-Conotoxin GVIA did not block either current. In contrast, at the neuromuscular junction, dihydropyridines reduced the amplitude of postsynaptic potentials by only a modest amount, whereas ω-Agatoxin IVA at doses as low as 64 nM reduced the amplitude of postsynaptic potentials almost entirely. These effects were presynaptic. ω-Conotoxin GVIA did not change the amplitude of postsynaptic potentials. The different pharmacological profiles of the two isolated preparations suggest that there are at least two different types of calcium channel in stomatogastric neurons and that ω-Agatoxin IVA and dihydropridines can be used to pharmacologically distinguish them.

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