Ion modulation of membrane permeability: effect of cations on intact cells and on cells and phospholipid bilayers treated with pore-forming agents.
Leakage of ions (Na+, K+) and phosphorylated metabolites (phosphorylcholine, 2-deoxyglucose 6-phosphate) through membrane lesions in intact cells or in cells modified by 'pore-forming' agent has been studied. Leakage from intact cells is induced by protons and by divalent cations such as Cu2+, Cd2+ or Zn2+. Leakage from agent-modified cells--or across phospholipid bilayers modified by agent--is prevented by low concentrations of the same cations and by higher concentrations of Ca2+, Mn2+ or Ba2+; Mg2+, dimethonium, spermine, or spermidine are virtually ineffective. The relative efficacy of a particular cation (e.g. Ca2+) depends more on cell type than on the nature of the pore-forming agent. The predominant effect is on binding of cation to specific sites, not on surface charge. Surface charge, on the other hand, does affect leakage from agent-modified cells in that suspension in nonionic media reduces leakage, which can be restored by increasing the ionic strength: univalent (Na+, K+, Rb+, NH4+) and divalent (Mg2+, dimethonium) cations are equally effective; addition of protons or divalent cations such as Zn2+ to this system inhibits leakage. From this and other evidence here presented it is concluded that leakage across membranes is modulated by the presence of endogenous anionic components: when these are in the ionized state, leakage is favored; when unionized (as a result of protonation) or chelated (by binding to divalent cation), leakage is prevented. It is suggested that such groups are exposed at the extracellular face of the plasma membrane.
Bashford
C L
CL
Department of Biochemistry, St. George's Hospital Medical School, London, United Kingdom.
Alder
G M
GM
Graham
J M
JM
Menestrina
G
G
Pasternak
C A
CA
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003300:Copper / Q000494:pharmacology; D004285:Dogs; D004553:Electric Conductivity; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D007477:Ions / Q000494:pharmacology*; D008051:Lipid Bilayers; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D017830:Octoxynol; D010222:Parainfluenza Virus 1, Human; D011092:Polyethylene Glycols / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D011522:Protons; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D010738:Type C Phospholipases / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D002413:Cations, Divalent; D007477:Ions; D008051:Lipid Bilayers; D011522:Protons; D002104:Cadmium; D008555:Melitten; D011107:Polylysine; D011092:Polyethylene Glycols; D003300:Copper; D017830:Octoxynol; D010738:Type C Phospholipases; D015032:Zinc; D002118:Calcium