A Novel Pathway for Ca++ Entry into Plasmodium falciparum-Infected Blood Cells

Sanjay A. Desai Departments of Cell Biology, Medicine, Pathology and Mechanical Engineering, Washington University, St. Louis, Missouri

Search for other papers by Sanjay A. Desai in
Current site
Google Scholar
PubMed
Close
,
Edwin W. McCleskey Departments of Cell Biology, Medicine, Pathology and Mechanical Engineering, Washington University, St. Louis, Missouri

Search for other papers by Edwin W. McCleskey in
Current site
Google Scholar
PubMed
Close
,
Paul H. Schlesinger Departments of Cell Biology, Medicine, Pathology and Mechanical Engineering, Washington University, St. Louis, Missouri

Search for other papers by Paul H. Schlesinger in
Current site
Google Scholar
PubMed
Close
, and
Donald J. Krogstad Departments of Cell Biology, Medicine, Pathology and Mechanical Engineering, Washington University, St. Louis, Missouri

Search for other papers by Donald J. Krogstad in
Current site
Google Scholar
PubMed
Close
Restricted access

Growth of the human malaria parasite, Plasmodium falciparum, within the red blood cell (RBC) requires external Ca++ and is associated with a markedly elevated intracellular Ca++ concentration, [Ca++]i. We used 45Ca++ flux studies and patch clamp recordings to examine the mechanisms responsible for this increased [Ca++]i. The 45Ca++ flux studies indicated that net Ca++ entry into parasitized RBCs (PRBCs) is 18 times faster than into unparasitized RBCs. This increased accumulation rate is too rapid to be explained by inhibition of the Ca++ extrusion pump, an ATPase that keeps the [Ca++]i of unparasitized RBCs exceedingly low. Acceleration of the preexisting Ca++ entry, mediated by a divalent cation carrier, also cannot explain Ca++ accumulation in PRBCs: there are fundamental differences in substrate preference and in the effects of external Ca++ on 45Ca++ efflux between unparasitized RBCs and PRBCs. Patch clamp of intact PRBC surface membranes revealed rare unitary channel openings not observed on unparasitized RBCs. With 80 mM CaCl2 in the patch pipette, this channel carried inward current, suggesting Ca++ entry at a rate comparable with the observed 45Ca++ flux. These data indicate that the malaria parasite induces a novel pathway in the host RBC membrane for Ca++ entry and suggest that this pathway is a Ca++-permeable channel.

Author Notes

Past two years Past Year Past 30 Days
Abstract Views 1843 1146 177
Full Text Views 48 16 0
PDF Downloads 51 17 0
 

 

 

 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save