The heavy metal ions Ag+ and Hg2+ trigger calcium release from cardiac sarcoplasmic reticulum

Academic Article

Abstract

  • Heavy metal ions have been shown to induce Ca release from skeletal sarcoplasmic reticulum (SR) by binding to free sulfhydryl groups on a Ca channel protein and are now examined in cardiac SR. Ag and Hg (at 10-25 μm) induced Ca release from isolated canine cardiac SR vesicles whereas Ni , Cd , and Cu had no effect at up to 200 μm. Ag -induced Ca release was measured in the presence of modulators of SR Ca release was compared to Ca -induced Ca release and was found to have the following characteristics, (i) Ag -induced Ca release was dependent on free [Mg ], such that rates of efflux from actively loaded SR vesicles increased by 40% in 0.2 to 1.0 mm Mg and decreased by 50% from 1.0 to 10.0 mm Mg . (ii) Ruthenium red (2-20 μm) and tetracaine (0.2-1.0 mm), known inhibitors of SR Ca release, inhibited Ag -induced Ca release, (iii) Adenine nucleotides such as cAMP (0.25-2.0 mm) enhanced Ca -induced Ca release, and stimulated Ag -induced Ca release. (iv) Low Ag to SR protein ratios (5-50 nmol Ag /mg protein) stimulated Ca -dependent ATPase activity in Triton X-100-uncoupled SR vesicles. (v) At higher ratios of Ag to SR proteins (50-250 nmol Ag /mg protein), the rate of Ca efflux declined and Ca -dependent ATPase activity decreased gradually, up to a maximum of 50% inhibition, (vi) Ag stimulated Ca efflux from passively loaded SR vesicles (i.e., in the absence of ATP and functional Ca pumps), indicating a site of action distinct from the SR Ca pump. Thus, at low Ag to SR protein ratios, Ag is very selective for the Ca release channel. At higher ratios, this selectivity declines as Ag also inhibits the activity of Ca ,Mg -ATPase pumps. Ag most likely binds to one or more sulfhydryl sites "on" or "adjacent" to the physiological Ca release channel in cardiac SR to induce Ca release. © 1990. 2+ 2+ + 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ + 2+ 2+ 2+ 2+ 2+ + 2+ 2+ 2+ + 2+ + + 2+ + + 2+ 2+ + 2+ 2+ 2+ 2+ 2+ 2+ + 2+ 2+ + 2+ 2+
  • Authors

    Digital Object Identifier (doi)

    Pubmed Id

  • 15546210
  • Author List

  • Prabhu SD; Salama G
  • Start Page

  • 47
  • End Page

  • 55
  • Volume

  • 277
  • Issue

  • 1