Specific Inhibition of the Plasmodial Surface Anion Channel by Dantrolene

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Malaria parasites are rapidly killed by dantrolene derivatives specific for the plasmodial surface anion channel.

Dantrolene was recently identified as a novel inhibitor of the plasmodial surface anion channel (PSAC), an unusual ion channel on Plasmodium falciparum-infected human red blood cells. Because dantrolene is used clinically, has a high therapeutic index, and has desirable chemical synthetic properties, it may be a lead compound for antimalarial development. However, dantrolene derivatives would n...

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Synergistic Malaria Parasite Killing by Two Types of Plasmodial Surface Anion Channel Inhibitors

Malaria parasites increase their host erythrocyte's permeability to a broad range of ions and organic solutes. The plasmodial surface anion channel (PSAC) mediates this uptake and is an established drug target. Development of therapies targeting this channel is limited by several problems including interactions between known inhibitors and permeating solutes that lead to incomplete channel bloc...

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Voltage-dependent inactivation of the plasmodial surface anion channel via a cleavable cytoplasmic component.

Erythrocytes infected with malaria parasites have increased permeability to ions and various nutrient solutes, mediated by a parasite ion channel known as the plasmodial surface anion channel (PSAC). The parasite clag3 gene family encodes PSAC activity, but there may also be additional unidentified components of this channel. Consistent with a lack of clag3 homology to genes of other ion channe...

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High Guanidinium Permeability Reveals Dehydration-Dependent Ion Selectivity in the Plasmodial Surface Anion Channel

Malaria parasites grow within vertebrate erythrocytes and increase host cell permeability to access nutrients from plasma. This increase is mediated by the plasmodial surface anion channel (PSAC), an unusual ion channel linked to the conserved clag gene family. Although PSAC recognizes and transports a broad range of uncharged and charged solutes, it must efficiently exclude the small Na(+) ion...

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Solute-inhibitor interactions in the plasmodial surface anion channel reveal complexities in the transport process.

Human red blood cells infected with the malaria parasite Plasmodium falciparum have markedly increased permeabilities to diverse organic and inorganic solutes. The plasmodial surface anion channel (PSAC), recently identified with electrophysiological methods, contributes to the uptake of many small solutes. In this study, we explored the effects of known PSAC antagonists on transport of differe...

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ژورنال

عنوان ژورنال: Eukaryotic Cell

سال: 2006

ISSN: 1535-9778,1535-9786

DOI: 10.1128/ec.00212-06