ω-conotoxin GVIA, ω-conotoxin GVIA blocks Cav2.2
- Known as:
- ω-conotoxin GVIA, ω-conotoxin GVIA blocks Cav2.2
- Catalog number:
- 08CON003-00500
- Product Quantity:
- 500 ug
- Category:
- -
- Supplier:
- Smartox
- Gene target:
- ω-conotoxin GVIA blocks Cav2.2
Related products to: ω-conotoxin GVIA, ω-conotoxin GVIA blocks Cav2.2
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- In many mammals, early interactions between caregivers and offspring involve rich physical contact during which offspring typically remain calm near the caregiver. Such contact is thought to support emotional regulation during infancy, but how prior experience shapes these mechanisms remains unclear. Here, we show that back stroking induces a calming response in human infants and mouse pups, with reduced movement. In mouse pups, back stroking further reduces heart rate, facilitates sleep onset, and attenuates stress-induced corticosterone elevations. These sleep-promoting and stress-buffering effects are absent in artificially reared pups deprived of postnatal maternal care, suggesting that early experience tunes the calming response to stroking. Transcriptomic analysis reveals reduced hypothalamic expression of the calcium channel subunit gene Cacna1b in artificially reared pups, and knockdown of hypothalamic Cacna1b in maternally reared pups abolishes stroking-induced calming. Thus, early-life maternal care and associated physical contact may shape hypothalamic circuits supporting behavioral and physiological regulation. - Source: PubMed
Publication date: 2026/04/10
Yoshida SachineHarauma AkikoMoriguchi ToruTsuneoka YousukeNarikiyo KimiyaMiyanishi KazuyaKashima MakotoWada MakotoHayashi YuFunato Hiromasa - Hepatocellular carcinoma (HCC) is a significant global health burden. Cancer cells often exhibit an imbalance in intracellular calcium homeostasis. This study aims to explore the relationship between calcium-related genes and the prognosis of HCC, and establish a prognostic model based on calcium-related genes. - Source: PubMed
Publication date: 2026/03/21
Chen YanlingMa YarongZhao GuoruiLi JianhaoZhang Guizhen - The spontaneous firing activity of substantia nigra (SN) dopaminergic (DA) neurons is finely tuned by the autocrine inhibition mediated by D2 DA autoreceptors (D2-ARs) that activate GIRK2 channels. Despite this regulatory mechanism, the vulnerability of SN DA neurons may nevertheless increase due to an altered spontaneous firing activity of DA neurons, Ca dishomeostasis, mitochondrial stress, high dendritic arborization, aggregation of α-synuclein (α-syn), α-syn mutations, reduced levels of calbindin protein, etc. Although the intraneuronal accumulation and the spreading of misfolded α-syn is a hallmark of full-blown Parkinson's disease, the effects produced by α-syn aggregation on neuronal functionality at the early onset of neurodegeneration are still of debate. We previously reported that α-syn oligomers in the extracellular medium drastically inhibit the firing rate of midbrain neurons and significantly impair burst generation and network synchronization. Here, by combining conventional electrophysiology and cutting-edge technology of micro-graphitized diamond micro-electrode arrays, we confirm that exogenous α-syn effectively slows down the firing rate of SN DA neurons, but it also selectively upregulates Cav2.2 (N-type) Ca currents and consequently Ca-dependent DA release. Thus, our data uncover a novel regulatory mechanism in SN DA neurons and demonstrate that exogenous α-syn alters the interplay among Ca entry, spontaneous firing and DA release causing DA accumulation in the extracellular milieu and intracellular Ca overload. Both processes may represent a target for future investigations to better understand the initial phases of SN DA neuron degeneration. KEY POINTS: We combined conventional electrophysiology and micro-graphitized diamond multi-electrode arrays to investigate the effect of exogeneous α-synuclein on cultured midbrain dopaminergic neurons isolated from substantia nigra. α-Synuclein oligomers slow down the firing rate of dopaminergic neurons and up-regulate Cav2.2 (N-type) Ca currents. Raised Cav2.2 currents in turn increase the depolarization-evoked dopamine release and the frequency of quantal exocytotic events. Overall, this mechanism causes dopamine accumulation in the extracellular milieu and intracellular Ca overload. - Source: PubMed
Publication date: 2026/03/16
Tomagra GiuliaBattaglia AnthonyFranchino ClaudioBonzano SaraPicollo FedericoChiantia Giuseppede Iure AntonioCalabresi PaoloPicconi BarbaraCarbone EmilioDe Marchis SilviaMarcantoni AndreaCarabelli Valentina - Voltage-gated Ca2.2 channels are essential for neurotransmitter release throughout the nervous system including areas related to learning and memory like the hippocampus. Previous results have shown that Ca2.2 channels are involved in cognitive processes. However, a link between alternative splicing of the (gene that encodes for Ca2.2) pre-mRNA and cognitive processes has not been described. The pre-mRNA undergoes extensive cell-specific alternative splicing. In this body of work, we focus on the cassette exon 18a. Alternative splicing of exon 18a generates two splice variants, +18a- and Δ18a-. Exon 18a encodes a 21-amino acid sequence within the SYNaptic PRotein INTeraction () site. Splice variants containing exon 18a (+18a-Ca2.2) show reduced cumulative inactivation and increased Ca current density compared to splice variants lacking exon 18a (Δ18a-Ca2.2), suggesting functional specialization. We previously showed that +18a- splice variants are enriched in cholecystokinin-expressing interneurons (CCKINs). This neuronal type is strongly implicated in associative learning. Therefore, we tested whether alternative splicing of exon 18a contributes to associative learning. To test this hypothesis, we used genetically engineered mice that constitutively express either +18a- (+18a) or Δ18a- (Δ18a). We first validated that restricted splicing of exon 18a did not alter downstream alternative or constitutive spliced exons in the pre-mRNA, nor total Ca2.2 protein levels. We then performed a comprehensive behavioral analysis that included assessment of associate learning. We found that in the trace fear conditioning task, +18a mice exhibited less freezing during the trace interval in both the acquisition and memory phases compared to WT mice. Whereas Δ18a mice showed enhanced freezing during the same intervals relative to WT mice. These bidirectional phenotypes reveal that exon 18a shapes aversive associative learning. Furthermore, exon 18a splicing did not influence spatial working memory, spatial navigation under stress, nociceptive responses in basal and inflammatory conditions, overall locomotion or exploratory behavior. These results suggest that the behavioral impact of exon 18a splicing is highly selective. Together, our findings identify alternative splicing of exon 18a as a molecular contributor to associative learning. - Source: PubMed
Publication date: 2026/02/17
Dhillon Simrat KaurCardarelli AvaBrennecke AshtonBradford AaronBunda AlexandraMacKenzie ForestTkachev VladimirCall ColinAndrade Arturo - Protein tyrosine phosphatase B (PtpB) is a virulence-associated phosphotyrosine phosphatase secreted by Mycobacterium tuberculosis (Mtb), known to disrupt host immune signaling by dephosphorylating key proteins. Targeting PtpB represents a rational strategy for anti-TB drug discovery. This study presents an integrative computational framework for identifying and evaluating small-molecule inhibitors of Mtb PtpB. QSAR models were constructed using four molecular fingerprint types, CDK, PubChem, MACCS, and AtomPairs2DCount, as regression models predicting pIC values. Multiple machine learning algorithms were evaluated, with model performance assessed via R, RMSE, cross-validation, and Y-randomization. SHAP analysis was applied to the top-performing PubChem-SVR model to interpret key structural features. Top-ranked compounds were subjected to molecular docking followed by 250 ns MD simulations to examine binding stability. MM-GBSA and PCA were used for post-simulation analysis. Gene-level interactions were evaluated by comparing predicted compound targets with Mtb-related host genes. Among descriptors, the PubChem-RF model achieved the best performance. SHAP identified PubchemFP417 (alkyne), PubchemFP462 (carboxylic acid), PubchemFP143 (five-membered rings), and PubchemFP34 (sulfur-containing fragments) as major contributors. CHEMBL4635765 showed strong and stable binding within the PTP pocket, while isoxazole carboxylic acid maintained key interactions but with lower stability. Network analysis revealed four shared targets (APP, HDAC8, CACNA1B, pvdQ) and compound-specific links to immune-related genes, including PTPN1 and NFKB1. This integrative computational study combines machine learning, structural modeling, and network pharmacology to provide mechanistic insights into PtpB inhibition and to identify promising chemical scaffolds for future anti-tubercular research. As the analysis is entirely computational, experimental validation will be required to confirm the predicted activities. - Source: PubMed
Publication date: 2026/02/18
Imran Mohd