Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using .omega.-conotoxin from Conus magus venom

Olivera, B.M.; Cruz, L J; Santos, Vanessa de Carla Batista dos; LeCheminant, Garth W.; Griffin, David C.; Zeikus, Regina D.; McIntosh, J. Michael; Galyean, Robert; Varga, Júlia; Gray, William R.

doi:10.1021/bi00382a004

Cited by 335 publications

(208 citation statements)

References 19 publications

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“…The cysteine topology of ␦-CTX TxVIA is similar to those of -conotoxin MVIIA (-CTX MVIIA) obtained from Conus magus (12) and -conotoxin GVIA (-CTX GVIA) from Conus geographus (13), which are specific antagonists for N-type calcium channels (see Fig. 1).…”

mentioning

confidence: 63%

Three-dimensional Solution Structure of the Sodium Channel Agonist/Antagonist δ-Conotoxin TxVIA

Kohno

Sasaki

Kobayashi

et al. 2002

Journal of Biological Chemistry

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The three-dimensional solution structure of ␦-conotoxin TxVIA, a 27-mer peptide agonist/antagonist of sodium channels, was determined by two-dimensional 1 H NMR spectroscopy with simulated annealing calculations. A total of 20 converged structures of ␦-conotoxin TxVIA were obtained on the basis of 360 distance constraints obtained from nuclear Overhauser effect connectivities, 28 torsion angle constraints, and 27 constraints associated with hydrogen bonds and disulfide bonds. The atomic root mean square difference about the averaged coordinate positions is 0.35 ؎ 0.07 Å for the backbone atoms (N, C ␣ , C) and 0.98 ؎ 0.14 Å for all heavy atoms of the entire peptide. The molecular structure of ␦-conotoxin TxVIA is composed of a short triplestranded antiparallel ␤-sheet. The overall ␤-sheet topology is ؉2x, ؊1, which is the same as those for other conotoxins. However, the three-dimensional structure of ␦-conotoxin TxVIA has an unusual hydrophobic patch on one side of the molecule, which may play an important role in the sodium channel binding. These results provide a molecular basis for understanding the mechanism of sodium channel modulation through the toxinchannel interaction and insight into the discrimination of different ion channels.

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confidence: 63%

Three-dimensional Solution Structure of the Sodium Channel Agonist/Antagonist δ-Conotoxin TxVIA

Kohno

Sasaki

Kobayashi

et al. 2002

Journal of Biological Chemistry

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“…3B, no significant change was observed in the amount of current sensitive to 500 nM v-conotoxin mVIIA, a Ca V 2.2 specific blocker, when Ca V 2.3 was expressed. 26 v-conotoxin mVIIA reduced the current in uninjected cells by 14 § 1 pA/pF (n D 9). A time course of block in an uninjected SCG neuron is shown in Fig.…”

Section: Resultsmentioning

confidence: 97%

Ca_V2 channel subtype expression in rat sympathetic neurons is selectively regulated by α₂δ subunits

Scott

Kammermeier

2017

Channels

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Type two voltage gated calcium (Ca V 2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability. 1 Mechanisms that regulate Ca V 2 channel expression at synapses have been studied extensively, which motivated us to perform similar studies in the soma. Rat sympathetic neurons from the superior cervical ganglion (SCG) natively express Ca V 2.2 and Ca V 2.3. 2 We noted previously that heterologous expression of Ca V 2.1 but not Ca V 2.2 results in increased calcium current in SCG neurons. 3 In the present study, we extended these observations to show that both Ca V 2.1 and Ca V 2.3 expression resulted in increased calcium currents while Ca V 2.2 expression did not. Further, Ca V 2.1 could displace native Ca V 2.2 channels, but Ca V 2.3 expression could not. Heterologous expression of the individual accessory subunits a 2 d-1, a 2 d-2, a 2 d-3, or b4 alone failed to increase current density, suggesting that the calcium current ceiling when Ca V 2.2 was over-expressed was not due to lack of these subunits. Interestingly, introduction of recombinant a2d subunits produced surprising effects on displacement of native Ca V 2.2 by recombinant channels. Both a 2 d-1 and a 2 d-2 seemed to promote Ca V 2.2 displacement by recombinant channel expression, while a 2 d-3 appeared to protect Ca V 2.2 from displacement. Thus, we observe a selective prioritization of Ca V channel functional expression in neurons by specific a 2 d subunits. These data highlight a new function for a 2 d subtypes that could shed light on subtype selectivity of Ca V 2 membrane expression.

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“…26,27 The 27-amino acid -conotoxin-GVIA peptide isolated from Conus geographus is a potent, selective, and irreversible inhibitor of N-type channels. Similarly, -conotoxin-MVIIA (called Prialt hereafter), a 25-amino acid peptide from the venom of Conus magnus is a potent blocker of N-type channels although acts in a reversible manner.…”

Section: N-type Calcium Channels As a Primary Therapeutic Target For mentioning

confidence: 99%

Targeting chronic and neuropathic pain: The N-type calcium channel comes of age

2005

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Summary:The rapid entry of calcium into cells through activation of voltage-gated calcium channels directly affects membrane potential and contributes to electrical excitability, repetitive firing patterns, excitation-contraction coupling, and gene expression. At presynaptic nerve terminals, calcium entry is the initial trigger mediating the release of neurotransmitters via the calcium-dependent fusion of synaptic vesicles and involves interactions with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex of synaptic release proteins. Physiological factors or drugs that affect either presynaptic calcium channel activity or the efficacy of calcium-dependent vesicle fusion have dramatic consequences on synaptic transmission, including that mediating pain signaling. The Ntype calcium channel exhibits a number of characteristics that make it an attractive target for therapeutic intervention concerning chronic and neuropathic pain conditions. Within the past year, both U.S. and European regulatory agencies have approved the use of the cationic peptide Prialt for the treatment of intractable pain. Prialt is the first N-type calcium channel blocker approved for clinical use and represents the first new proven mechanism of action for chronic pain intervention in many years. The present review discusses the rationale behind targeting the N-type calcium channel, some of the limitations confronting the widespread clinical application of Prialt, and outlines possible strategies to improve upon Prialt's relatively narrow therapeutic window.

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Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using .omega.-conotoxin from Conus magus venom

Cited by 335 publications

References 19 publications

Three-dimensional Solution Structure of the Sodium Channel Agonist/Antagonist δ-Conotoxin TxVIA

Three-dimensional Solution Structure of the Sodium Channel Agonist/Antagonist δ-Conotoxin TxVIA

Ca_V2 channel subtype expression in rat sympathetic neurons is selectively regulated by α₂δ subunits

Targeting chronic and neuropathic pain: The N-type calcium channel comes of age

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Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using .omega.-conotoxin from Conus magus venom

Cited by 335 publications

References 19 publications

Three-dimensional Solution Structure of the Sodium Channel Agonist/Antagonist δ-Conotoxin TxVIA

Three-dimensional Solution Structure of the Sodium Channel Agonist/Antagonist δ-Conotoxin TxVIA

CaV2 channel subtype expression in rat sympathetic neurons is selectively regulated by α2δ subunits

Targeting chronic and neuropathic pain: The N-type calcium channel comes of age

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Ca_V2 channel subtype expression in rat sympathetic neurons is selectively regulated by α₂δ subunits