Comparative action of methylmercury and divalent inorganic mercury on nerve terminal and intraterminal mitochondrial membrane potentials.
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 microM) 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 microM 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Hare
M F
MF
Department of Pharmacology and Toxicology, Michigan State University, East Lansing.
Atchison
W D
WD
D000818:Animals; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D008628:Mercury / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects
D008767:Methylmercury Compounds; D008628:Mercury