Comparative characterization of two scorpion toxins, BlTx1 and BlTx2, identifies BlTx2 as a Kv4.1-selective peptide

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  Comparative characterization of two scorpion toxins, BlTx1 and BlTx2, identifies BlTx2 as a Kv4.1-selective peptide Abstract Voltage-gated potassium channels of the Kv4 subfamily (Kv4.1, Kv4.2, and Kv4.3) mediate transient A-type potassium currents that regulate neuronal excitability, dendritic integration, and cardiac repolarization. Despite their importance, no pharmacological tool has been available to selectively dissect the role of Kv4.1, as existing peptide toxins from the α-KTx15 family display broad activity across Kv4 isoforms. Here, we report the discovery and characterization of two novel scorpion toxins, BlTx1 and BlTx2, isolated from the venom gland transcriptome of  Buthacus leptochelys . Both toxins were heterologously expressed in yeast and purified to homogeneity. Electrophysiological recordings from  Xenopus laevis  oocytes revealed that BlTx1 and BlTx2 potently inhibited Kv4.1 currents, while sparing Kv4.2 and Kv4.3. Among a panel of 20 tested po...

Scorpion Envenoming as an Emerging Public Health Problem in Paraguay, Bolivia, and Midwest Brazil: Involvement of Tityus confluens and the Need for a Panregional Evaluation of Available Antivenoms

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Scorpion Envenoming as an Emerging Public Health Problem in Paraguay, Bolivia, and Midwest Brazil: Involvement of Tityus confluens and the Need for a Panregional Evaluation of Available Antivenoms

This contribution highlights the emergence of a newly endemic region for scorpion envenoming in South America, covering eastern Bolivia, Paraguay, and the midwestern Brazilian states of Mato Grosso and Mato Grosso do Sul. These areas have not historically been known to harbor life-threatening scorpion species. Tityus confluens, a parthenogenetic species of medical significance in Argentina, has been identified in severe and lethal human cases in Bolivia and Paraguay. Given that the clinical use of scorpion antivenom preparations in the region has often lacked preclinical data and considering the significant burden of scorpion envenoming, we propose a panregional evaluation of available anti-Tityus antivenoms. This evaluation, along with interdisciplinary efforts at a multinational scale to control scorpionism, aims to determine their true neutralization capacity and potential clinical efficacy against known culprits in the Southern Cone of South America and other regions endemic for scorpion envenoming on the continent.

Borges, Adolfo, Antonieta Rojas de Arias, Ana María Montaño, and Cláudio Mauricio V. de Souza. "Scorpion Envenoming as an Emerging Public Health Problem in Paraguay, Bolivia, and Midwest Brazil: Involvement of Tityus confluens and the Need for a Panregional Evaluation of Available Antivenoms", The American Journal of Tropical Medicine and Hygiene (published online ahead of print 2024), tpmd240424, accessed Oct 9, 2024, https://doi.org/10.4269/ajtmh.24-0424