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Journal ArticleDOI

A nutrient-permeable channel on the intraerythrocytic malaria parasite

TLDR
A 140-pS channel which is permeable to both cations and anions was identified on the parasitophorous vacuole membrane, the outer of the two membranes that separate the parasite from the erythrocyte cytosol, and may be essential for fulfilling the parasite's metabolic demands.
Abstract
During its 48-hour cycle inside the red blood cell, the human malaria parasite, Plasmodium falciparum, increases its volume 25-fold and divides asexually. This rapid growth demands large amounts of nutrients, a problem exacerbated by the lower metabolic rate and relative ionic impermeability of the host red blood cell. Direct passage of small nutrients across the two membranes that separate the parasite from the erythrocyte cytosol may be important for parasite development and has been demonstrated for radiolabelled glucose, amino acids, and purine nucleosides. Flux studies on plasmodia are limited, however, to suspensions of erythrocyte-free parasites and so cannot be used to examine the individual transport properties of the two membranes involved. Here we use the cell-attached patch clamp method to overcome this limitation. After removing the intervening red blood cell membrane and forming gigaohm seals on the small (3-5 microns) parasite, we studied transport across the parasitophorous vacuole membrane (PVM), the outer of the two membranes that separate the parasite from the erythrocyte cytosol. A 140-pS channel which is permeable to both cations and anions was identified on the PVM. This channel is present at high density, is open more than 98 per cent of the time at the resting potential of the PVM, and is permeable to lysine and glucuronate. The channel can readily transport amino acids and monosaccharides across the PVM and may be essential for fulfilling the parasite's metabolic demands.

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Citations
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Journal ArticleDOI

Membrane Transport in the Malaria-Infected Erythrocyte

TL;DR: This review focuses on the transport properties of the different membranes of the malaria-infected erythrocyte, as well as on the role played by the various membrane transport systems in the uptake of solutes from the extracellular medium, the disposal of metabolic wastes, and the origin and maintenance of electrochemical ion gradients.
Journal ArticleDOI

Attenuation of and protection induced by a leucine auxotroph of Mycobacterium tuberculosis

TL;DR: Attenuated mutants of Mycobacterium tuberculosisrepresent potential vaccine candidates for the prevention of tuberculosis and challenge can be achieved with a leucine auxotroph and it is suggested that to induce optimal protection, attenuated strains of M. tuberculosis should persist long enough and be sufficiently metabolically active to synthesize relevant antigens for an extended period of time.
Journal ArticleDOI

Distinct external signals trigger sequential release of apical organelles during erythrocyte invasion by malaria parasites.

TL;DR: The results identify for the first time the external signals responsible for the sequential release of microneme and rhoptry proteins during erythrocyte invasion and provide a starting point for the dissection of signal transduction pathways involved in regulated exocytosis of these key apical organelles.
Journal ArticleDOI

A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite.

TL;DR: The permeability of infected RBCs is studied using the whole-cell voltage-clamp method and a small (< 10 pS) ion channel on the infected RBC surface is confirmed, indicating that it may have a primary role in a sequential diffusive pathway for parasite nutrient acquisition.
Journal ArticleDOI

Morphology and kinetics of the three distinct phases of red blood cell invasion by Plasmodium falciparum merozoites.

TL;DR: Video microscopy is used to address the kinetics of RBC invasion in the human malaria parasite Plasmodium falciparum and provides a morphological and kinetic framework onto which the invasion-associated physiological and molecular events can be overlaid.
References
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Journal ArticleDOI

Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.

TL;DR: The extracellular patch clamp method, which first allowed the detection of single channel currents in biological membranes, has been further refined to enable higher current resolution, direct membrane patch potential control, and physical isolation of membrane patches.
Journal ArticleDOI

Human malaria parasites in continuous culture

TL;DR: Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen.
Journal ArticleDOI

Synchronization of Plasmodium falciparum erythrocytic stages in culture.

TL;DR: Synchronous development of the erythrocytic stages of a human malaria parasite, Plasmodium falciparum, in culture was accomplished by suspending cultured parasites in 5% D-sorbitol and subsequent reintroduction into culture.
Journal ArticleDOI

Gap junctions: new tools, new answers, new questions.

TL;DR: The big news is that gap junctions of different kinds are formed by a number of homologous proteins termed connexins, which are encoded by a gene family.
Journal ArticleDOI

Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites.

A. F. G. Slater, +1 more
- 09 Jan 1992 - 
TL;DR: The identification and characterization of a haem polymerase enzyme activity from extracts of Plasmodium fal-ciparum trophozoites are reported and show that this enzyme is inhibited by quinoline-containing drugs such as chloroquine and quinine, providing a possible explanation for the highly stage-specific anti-malarial properties of these drugs.
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