title: Depletion of calcium stores by thapsigargin induces membrane depolarization by cation entry in human neutrophils.
abstract: The ability of various cations to change the electrical potential of the plasma membrane was examined in human neutrophils by the use of the fluorescent cationic dye 3,3'-dipropylthiadicarbocyanine. When the cells were suspended in 140 mM KCl, the fluorescence was high, indicating depolarized neutrophils. Suspension in 145 mM N-methyl-D-glucamine chloride (NMG), replacing sodium and potassium chloride, resulted in hyperpolarized neutrophils. After depletion of the intracellular calcium stores of the NMG-suspended cells with thapsigargin and EDTA or EGTA, the addition of cations depolarized the neutrophils, suggesting the existence of pathways for cation entry. Besides Na+ and K+, several divalent cations were effective in the sequence: Ca2+ > Mn2+ > Ba2+ > Cd2+ > Mg2+ > Co2+ > Zn2+ > Ni2+. Pretreatment of the neutrophils with 0.5 or 1 mM CaCl2, resulting in loading of calcium stores, reduced the ability of some of the cations to depolarize the NMG-suspended cells. From the depolarizing effects of the cations it is concluded that the entries of Ca2+, Mg2+, Mn2+, Ba2+, probably Co2+, to some extent Na+ and K+, but hardly Cd2+, Zn2+, or Ni2+, are regulated by the filling state of the intracellular calcium stores in human neutrophils. The store-regulated entry pathway may contribute to the control of the membrane potential and become active when the neutrophils are stimulated.
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Scharff
authors.forename: B
authors.initials: B
authors.lastname: Foder
mesh_terms: D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009504:Neutrophils / Q000737:chemistry / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002413:Cations, Divalent; D005456:Fluorescent Dyes; D001464:Barium; D019284:Thapsigargin; D008274:Magnesium; D002118:Calcium