scholarly journals Characterisation of δ-Conotoxin TxVIA as a Mammalian T-Type Calcium Channel Modulator

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 343
Author(s):  
Dan Wang ◽  
S.W.A. Himaya ◽  
Jean Giacomotto ◽  
Md. Mahadhi Hasan ◽  
Fernanda C. Cardoso ◽  
...  
Keyword(s):  
Amino Acid ◽  
Ion Channel ◽  
Calcium Channel ◽  
Binding Sites ◽  
Molluscan Neurons ◽  
Cone Snail ◽  
Voltage Gated ◽  
Channel Inactivation ◽  
High Concentrations ◽  
Channel Modulator

The 27-amino acid (aa)-long δ-conotoxin TxVIA, originally isolated from the mollusc-hunting cone snail Conus textile, slows voltage-gated sodium (NaV) channel inactivation in molluscan neurons, but its mammalian ion channel targets remain undetermined. In this study, we confirmed that TxVIA was inactive on mammalian NaV1.2 and NaV1.7 even at high concentrations (10 µM). Given the fact that invertebrate NaV channel and T-type calcium channels (CaV3.x) are evolutionarily related, we examined the possibility that TxVIA may act on CaV3.x. Electrophysiological characterisation of the native TxVIA on CaV3.1, 3.2 and 3.3 revealed that TxVIA preferentially inhibits CaV3.2 current (IC50 = 0.24 μM) and enhances CaV3.1 current at higher concentrations. In fish bioassays TxVIA showed little effect on zebrafish behaviours when injected intramuscular at 250 ng/100 mg fish. The binding sites for TxVIA at NaV1.7 and CaV3.1 revealed that their channel binding sites contained a common epitope.

scholarly journals Insights into the structure and function of HV1 from a meta-analysis of mutation studies

2016 ◽  
Vol 148 (2) ◽  
pp. 97-118 ◽  
Author(s):  
Thomas E. DeCoursey ◽  
Deri Morgan ◽  
Boris Musset ◽  
Vladimir V. Cherny
Keyword(s):  
Amino Acid ◽  
Ion Channel ◽  
Meta Analysis ◽  
Structure And Function ◽  
Proton Channel ◽  
Vast Array ◽  
Voltage Gated ◽  
Interspecies Differences ◽  
And Function ◽  
Sheer Number

The voltage-gated proton channel (HV1) is a widely distributed, proton-specific ion channel with unique properties. Since 2006, when genes for HV1 were identified, a vast array of mutations have been generated and characterized. Accessing this potentially useful resource is hindered, however, by the sheer number of mutations and interspecies differences in amino acid numbering. This review organizes all existing information in a logical manner to allow swift identification of studies that have characterized any particular mutation. Although much can be gained from this meta-analysis, important questions about the inner workings of HV1 await future revelation.

CACNA1H antibodies associated with headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL)

Cephalalgia ◽  
2012 ◽  
Vol 33 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Murat Kürtüncü ◽  
Dilaver Kaya ◽  
Luigi Zuliani ◽  
Ece Erdağ ◽  
Sema İçöz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Ion Channel ◽  
Calcium Channel ◽  
High Titer ◽  
Neurological Symptoms ◽  
Neurological Deficits ◽  
Enzyme Linked Immunosorbent Assay ◽  
Voltage Gated ◽  
A Subunit ◽  
Protein Macroarray

Background Patients with the syndrome of headache with neurological deficits and lymphocytosis (HaNDL) typically present with recurrent and temporary attacks of neurological symptoms and cerebrospinal fluid lymphocytosis. Aim and methods To identify potential HaNDL‐associated antibodies directed against neuronal surface and/or synapse antigens, sera of four HaNDL patients and controls were screened with indirect immunohistochemistry, immunofluorescence, cell-based assay, radioimmunoassay, protein macroarray and enzyme-linked immunosorbent assay (ELISA). Results Although HaNDL sera did not yield antibodies to any of the well-characterized neuronal surface or synapse antigens, protein macroarray and ELISA studies showed high-titer antibodies to a subunit of the T-type voltage-gated calcium channel (VGCC), CACNA1H, in sera of two HaNDL patients. Conclusion Our results support the notion that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis and occurrence of neurological symptoms.

Identification of a second region of the beta-subunit involved in regulation of calcium channel inactivation

1996 ◽  
Vol 271 (5) ◽  
pp. C1539-C1545 ◽  
Author(s):  
N. Qin ◽  
R. Olcese ◽  
J. Zhou ◽  
O. A. Cabello ◽  
L. Birnbaumer ◽  
...  
Keyword(s):  
Amino Acid ◽  
Calcium Channel ◽  
Splice Variants ◽  
Terminal Segment ◽  
Beta Subunit ◽  
Beta Subunits ◽  
High Sequence Identity ◽  
Channel Inactivation ◽  
Calcium Channel Inactivation ◽  
Common Effect

Previous studies have shown that NH2 termini of the type 1 and 2 beta-subunits modulate the rate at which the neuronal alpha 1E calcium channel inactivates in response to voltage and that they do so independently of their common effect to stimulate activation by voltage (R. Olcese, N. Qin, T. Schneider, A. Neely, X. Wei, E. Stefani, and L. Birnbaumer, Neuron 13: 1433-1438, 1994). By constructing NH2-terminal deletions of several splice variants of beta-subunits, we have now found differences in the way they affect the rate of alpha 1E inactivation that lead us to identify a second domain that also regulates the rate of voltage-induced inactivation of the Ca2+ channel. This second domain, named segment 3, lies between two regions of high-sequence identity between all known beta-subunits and exists in two lengths (long and short), each encoded in a separate exon. Beta-Subunits with the longer 45- to 53-amino acid version cause the channel to inactivate more slowly than subunits with the shorter 7-amino acid version. As is the case for the NH2 terminus, the segment 3 does not affect the regulation of channel activation by the beta-subunit. In addition, the effect of the NH2-terminal segment prevails over that of the internal segment. This raises the possibility that phosphorylation, other types of posttranslational modification, or interaction with other auxiliary calcium channel subunits may be necessary to unmask the regulatory effect of the internal segment.

scholarly journals Ion-channel blocker sensitivity of voltage-gated calcium-channel homologue Cch1 in Saccharomyces cerevisiae

Microbiology ◽  
2008 ◽  
Vol 154 (12) ◽  
pp. 3775-3781 ◽  
Author(s):  
Jinfeng Teng ◽  
Rika Goto ◽  
Kazuko Iida ◽  
Itaru Kojima ◽  
Hidetoshi Iida
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ion Channel ◽  
Calcium Channel ◽  
Channel Blocker ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channel

scholarly journals Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus

2015 ◽  
Vol 112 (16) ◽  
pp. 5087-5092 ◽  
Author(s):  
Joseph W. Aman ◽  
Julita S. Imperial ◽  
Beatrix Ueberheide ◽  
Min-Min Zhang ◽  
Manuel Aguilar ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Molecular Mechanisms ◽  
Prey Capture ◽  
Sequence Similarity ◽  
Cone Snail ◽  
Evolutionary Transitions ◽  
Voltage Gated ◽  
Channel Inactivation ◽  
Voltage Gated Sodium Channels ◽  
Cone Snails

Prey shifts in carnivorous predators are events that can initiate the accelerated generation of new biodiversity. However, it is seldom possible to reconstruct how the change in prey preference occurred. Here we describe an evolutionary “smoking gun” that illuminates the transition from worm hunting to fish hunting among marine cone snails, resulting in the adaptive radiation of fish-hunting lineages comprising ∼100 piscivorous Conus species. This smoking gun is δ-conotoxin TsVIA, a peptide from the venom of Conus tessulatus that delays inactivation of vertebrate voltage-gated sodium channels. C. tessulatus is a species in a worm-hunting clade, which is phylogenetically closely related to the fish-hunting cone snail specialists. The discovery of a δ-conotoxin that potently acts on vertebrate sodium channels in the venom of a worm-hunting cone snail suggests that a closely related ancestral toxin enabled the transition from worm hunting to fish hunting, as δ-conotoxins are highly conserved among fish hunters and critical to their mechanism of prey capture; this peptide, δ-conotoxin TsVIA, has striking sequence similarity to these δ-conotoxins from piscivorous cone snail venoms. Calcium-imaging studies on dissociated dorsal root ganglion (DRG) neurons revealed the peptide’s putative molecular target (voltage-gated sodium channels) and mechanism of action (inhibition of channel inactivation). The results were confirmed by electrophysiology. This work demonstrates how elucidating the specific interactions between toxins and receptors from phylogenetically well-defined lineages can uncover molecular mechanisms that underlie significant evolutionary transitions.

scholarly journals Weaver granule neurons are rescued by calcium channel antagonists and antibodies against a neurite outgrowth domain of the B2 chain of laminin.

1996 ◽  
Vol 134 (2) ◽  
pp. 477-486 ◽  
Author(s):  
P Liesi ◽  
J M Wright
Keyword(s):  
Calcium Channel ◽  
Neurite Outgrowth ◽  
Calcium Channel Blocker ◽  
Neuronal Migration ◽  
Channel Blocker ◽  
Postnatal Life ◽  
Granule Neurons ◽  
Mk 801 ◽  
Voltage Gated ◽  
High Concentrations

The weaver mutation impairs migration of the cerebellar granular neurons and induces neuronal death during the first two weeks of postnatal life. To elucidate the molecular mechanisms for the impaired neuronal migration, we investigated the rescue mechanisms of the weaver (wv/wv) granule neurons in vitro. We found that Fab2 fragments of antibodies against a neurite outgrowth domain of the B2 chain of laminin enhanced neurite outgrowth and neuronal migration of the weaver granule neurons on a laminin substratum and in the established cable culture system. The rescue of the weaver granule neurons by antibodies against the B2 chain of laminin may result from the neutralizing effect of these antibodies against the elevated B2 chain levels of the weaver brain. The L-type calcium channel blocker, verapamil (1-5 microM), also rescued the weaver granule neurons. High concentrations of MK-801 (10-20 microM), a glutamate receptor antagonist and voltage-gated calcium channel blocker, rescued the weaver granule neurons similar to verapamil, but low concentrations of MK-801 (1 microM) had no rescue effect. Simultaneous patch-clamp studies indicated that the weaver granule neurons did not express functional N-methyl-D-aspartate receptors further indicating that the rescue of the weaver granule neurons by MK-801 resulted from its known inhibition of voltage-gated calcium channels. The present results indicate that antibodies against the B2 chain of laminin, verapamil, and high concentrations of MK-801 protect the weaver granule neurons from the otherwise destructive action of the weaver gene. Thus, both the laminin system and calcium channel function contribute to the migration deficiency of the weaver granule neurons.

Sign in / Sign up

Export Citation Format

Share Document