ArticleEukaryotic cell2006
Specific inhibition of the plasmodial surface anion channel by dantrolene.
Article in Eukaryotic cell, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Recent Progress in the Development of New Antimalarial Drugs with Novel Targets.Drug design, development and therapy · 2020Review
- Malaria parasite proteins involved in nutrient channels at the host erythrocyte membrane: advances and questions for future research.International journal of current multidisciplinary studies · 2017Article
- Maduramicin Rapidly Eliminates Malaria Parasites and Potentiates the Gametocytocidal Activity of the Pyrazoleamide PA21A050.Antimicrobial agents and chemotherapy · 2015Article
- Potent Plasmodium falciparum gametocytocidal activity of diaminonaphthoquinones, lead antimalarial chemotypes identified in an antimalarial compound screen.Antimicrobial agents and chemotherapy · 2015Article
- Potent antimalarial activity of acriflavine in vitro and in vivo.ACS chemical biology · 2014Article
- Why do malaria parasites increase host erythrocyte permeability?Trends in parasitology · 2014Review
- Solute restriction reveals an essential role for clag3-associated channels in malaria parasite nutrient acquisition.Molecular pharmacology · 2012Article
- Ion and nutrient uptake by malaria parasite-infected erythrocytes.Cellular microbiology · 2012Review
- Identification of intracellular and plasma membrane calcium channel homologues in pathogenic parasites.PloS one · 2011Article
- A cell-based high-throughput screen validates the plasmodial surface anion channel as an antimalarial target.Molecular pharmacology · 2010Article
- Uptake of purines in Plasmodium falciparum-infected human erythrocytes is mostly mediated by the human equilibrative nucleoside transporter and the human facilitative nucleobase transporter.Malaria journal · 2010Article
- Malaria parasite mutants with altered erythrocyte permeability: a new drug resistance mechanism and important molecular tool.Future microbiology · 2010Review
- Complex inheritance of the plasmodial surface anion channel in a Plasmodium falciparum genetic cross.Molecular microbiology · 2009Article
- Changes in the plasmodial surface anion channel reduce leupeptin uptake and can confer drug resistance in Plasmodium falciparum-infected erythrocytes.Antimicrobial agents and chemotherapy · 2008Article
- Selective killing of the human malaria parasite Plasmodium falciparum by a benzylthiazolium dye.Experimental parasitology · 2007Article
- A blasticidin S-resistant Plasmodium falciparum mutant with a defective plasmodial surface anion channel.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Two distinct mechanisms of transport through the plasmodial surface anion channel.The Journal of membrane biologyArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The plasmodial surface anion channel (PSAC), induced on human erythrocytes by the malaria parasite Plasmodium falciparum, is an important target for antimalarial drug development because it may contribute to parasite nutrient acquisition. However, known antagonists of this channel are quite nonspecific, inhibiting many other channels and carriers. This lack of specificity not only complicates drug development but also raises doubts about the exact role of PSAC in the well-known parasite-induced permeability changes. We recently identified a family of new PSAC antagonists structurally related to dantrolene, an antagonist of muscle Ca++ release channels. Here, we explored the mechanism of dantrolene's actions on parasite-induced permeability changes. We found that dantrolene inhibits the increased permeabilities of sorbitol, two amino acids, an organic cation, and hypoxanthine, suggesting a common pathway shared by these diverse solutes. It also produced parallel reductions in PSAC single-channel and whole-cell Cl- currents. In contrast to its effect on parasite-induced permeabilities, dantrolene had no measurable effect on five other classes of anion channels, allaying concerns of poor specificity inherent to other known antagonists. Our studies indicate that dantrolene binds PSAC at an extracellular site distinct from the pore, where it inhibits the conformational changes required for channel gating. Its affinity for this site depends on ionic strength, implicating electrostatic interactions in dantrolene binding. In addition to the potential therapeutic applications of its derivatives, dantrolene's specificity and its defined mechanism of action on PSAC make it a useful tool for transport studies of infected erythrocytes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.