COMPARATIVE ACTION OF METHYLMERCURY AND DIVALENT INORGANIC MERCURY ON NERVE-TERMINAL AND INTRATERMINAL MITOCHONDRIAL-MEMBRANE POTENTIALS

  • 1 April 1992
    • journal article
    • research article
    • Vol. 261  (1) , 166-172
Abstract
Both methylmercury (MeHg) and inorganic divalent mercury (Hg++) alter the flux of ions and small molecules across nerve terminal membranes by mechanisms that may involve membrane depolarization. We compared the effects of MeHg and Hg++ on plasma (PSI(p)) and mitochondrial membrane potentials (PSI(m)) in synaptosomes using the potentiometric carbocyanine dye 3,3'-diethylthiadicarbocyanine iodide [diS-C2(5)]. Both mercurials (1-20-mu-M) produced concentration-dependent increases in dye fluorescence after 5 min of exposure which were not altered by removal of Ca++ from the medium. To determine directly effects of mercurials on PSI(p), predepolarization of PSI(m) using NaN3 and oligomycin was necessary. Under this condition, MeHg- and Hg++-induced increases in fluorescence were associated with depolarization of PSI(p). A second approach was used to assess changes in PSI(p). In synaptosomes, the magnitude of the increase in fluorescence resulting from depolarization of PSI(p) with a stimulus of constant intensity is a function of the resting PSI(p). The fluorescence response to depolarization of synaptosomes previously exposed to either MeHg or Hg++ (1-20-mu-M each) was reduced in a concentration-dependent manner relative to mercury-free controls. The concentration-dependent depolarization of PSI(p) calculated in this manner correlated (r = 0.958) with calculations of PSI(p) using direct measurements of increases in fluorescence intensity. MeHg- and Hg++-induced depolarizations were not altered by lowering Na+e or by the addition of the Na+ and Ca++ channel blockers tetrodotoxin and Co++, respectively. Thus, the effects of these two neurotoxic mercurials on synaptosomal membrane potentials were similar with respect to their loci but differed in magnitude. MeHg depolarized PSI(p) at concentrations of 10-mu-M or greater and depolarized PSI(m) at 20-mu-M. Hg++ produced significant depolarizations of PSI(p) at 5-mu-M and more potent effects than MeHg on both PSI(p) and PSI(m) at 10-mu-M or greater.