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• W2948506585 abstract "Trypanosoma cruzi is the causative agent of Chagas disease. The only two drugs accepted for the treatment of this infection are benznidazole and nifurtimox, which are of limited use in the predominant chronic phase. On the search for new drugs, the intracellular Ca 2+ regulation has been postulated as a possible target, due to differences found between host cells and the parasite. The mechanisms involved in the intracellular Ca 2+ regulation of T. cruzi have been partially elucidated. However, nothing is known about a putative channel responsible for the Ca 2+ entry into this parasite. In contrast, in Leishmania spp., a closely related hemoflagelate, a sphingosine‐activated plasma membrane Ca 2+ channel has been recently described. The latter resembles the L‐type voltage‐gated Ca 2+ channel present in humans, but with distinct characteristics. This channel is one of the main targets concerning the mechanism of action of miltefosine, the unique oral drug approved against leishmaniasis. In the present work, we describe for the first time, the electrophysiological characterization of a sphingosine‐activated Ca 2+ channel of T. cruzi by reconstituting plasma membrane vesicles into giant liposomes and patch clamp. This channel shares some characteristic as activation by Bay K8644 and inhibition by channel blockers such as nifedipine. However, the T. cruzi channel differs from the L‐type VGCC in its activation by sphingosine and/or miltefosine. Albeit the conductance for each, Ba 2+ , Ca 2+ and Sr 2+ was similar, the parasite channel appears not to be voltage dependent. A gene that presents homology in critical amino acids with its human ortholog Ca 2+ channel was identified." @default.
• W2948506585 created "2019-06-14" @default.
• W2948506585 creator A5004415199 @default.
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• W2948506585 date "2019-06-28" @default.
• W2948506585 modified "2023-10-17" @default.
• W2948506585 title "Identification and electrophysiological properties of a sphingosine‐dependent plasma membrane Ca²⁺ channel in <i>Trypanosoma cruzi</i>" @default.
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• W2948506585 doi "https://doi.org/10.1111/febs.14947" @default.
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