The membrane potential of the intraerythrocytic malaria parasite Plasmodium falciparum.
The membrane potential (Deltapsi) of the mature asexual form of the human malaria parasite, Plasmodium falciparum, isolated from its host erythrocyte using a saponin permeabilization technique, was investigated using both the radiolabeled Deltapsi indicator tetraphenylphosphonium ([(3)H]TPP(+)) and the fluorescent Deltapsi indicator DiBAC(4)(3) (bis-oxonol). For isolated parasites suspended in a high Na(+), low K(+) solution, Deltapsi was estimated from the measured distribution of [(3)H]TPP(+) to be -95 +/- 2 mV. Deltapsi was reduced by the specific V-type H(+) pump inhibitor bafilomycin A(1), by the H(+) ionophore CCCP, and by glucose deprivation. Acidification of the parasite cytosol (induced by the addition of lactate) resulted in a transient hyperpolarization, whereas a cytosolic alkalinization (induced by the addition of NH(4)(+)) resulted in a transient depolarization. A decrease in the extracellular pH resulted in a membrane depolarization, whereas an increase in the extracellular pH resulted in a membrane hyperpolarization. The parasite plasma membrane depolarized in response to an increase in the extracellular K(+) concentration and hyperpolarized in response to a decrease in the extracellular K(+) concentration and to the addition of the K(+) channel blockers Ba(2+) or Cs(+) to the suspending medium. The data are consistent with Deltapsi of the intraerythrocytic P. falciparum trophozoite being due to the electrogenic extrusion of H(+) via the V-type H(+) pump at the parasite surface. The current associated with the efflux of H(+) is countered, in part, by the influx of K(+) via Ba(2+)- and Cs(+)-sensitive K(+) channels in the parasite plasma membrane.
Allen
Richard J W
RJ
School of Biochemistry and Molecular Biology, Faculty of Science, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
Kirk
Kiaran
K
D000818:Animals; D001463:Barbiturates / Q000737:chemistry; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology; D005456:Fluorescent Dyes / Q000737:chemistry; D005947:Glucose / Q000378:metabolism; D007476:Ionophores; D007555:Isoxazoles / Q000737:chemistry; D018942:Macrolides / Q000494:pharmacology; D008564:Membrane Potentials; D009861:Onium Compounds / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D010963:Plasmodium falciparum / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects
D001463:Barbiturates; D005456:Fluorescent Dyes; D007476:Ionophores; D007555:Isoxazoles; D018942:Macrolides; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D015221:Potassium Channels; C052795:bis(1,3-dibutylbarbiturate)trimethine oxonol; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C040929:bafilomycin A1; D005947:Glucose; C013289:tetraphenylphosphonium