Celhdar and Molecular Neurobiology, Vot. 14. No. 6, 1994 Inhibitory Effects of HgC12 on Excitation- Secretion Coupling at the Motor Nerve Terminal and Excitation-Contraction Coupling in the Muscle Cell Asbjorn Roed ~ and Bente Brokstad Herlofson ~ Received September 21, 1993; accepted July 12, 1994 KEY WORDS: Mercuric chloride; methylmercuricchloride; caffeine;dantrolene; excitation-secretion coupling; excitation-contraction coupling. SUMMARY 1. Indirect and direct twitch (0.1-Hz) stimulation of the rat phrenic nerve- diaphragm disclosed that the inhibitory effect of HgC12, 3.7 x 10 .5 M, on the neuromuscular transmission and in the muscle cell, was accelerated by 10-sec periods of 50-Hz tetanic stimulation every 10min. This activity-dependent enhancement suggested an inhibitory mechanism of HgC12 related to the development of fatigue, like membrane depolarization or decreased excitability, decreased availability of transmitter, or interference with the factors controlling excitation-secretion coupling of the nerve terminal, i.e. (Ca2÷)0 or (Ca2÷)~, and excitation-contraction coupling in the muscle cell, i.e., (Ca2+)~. 2. During both indirect and direct stimulation, HgCl2-induced inhibition was enhanced markedly by pretreatment with caffeine, which releases Ca 2÷ from endoplasmic and sarcoplasmic reticulum in the nerve terminal and muscle cell, respectively. This caffeine-induced enhancement was completely antagonized by dantrolene, which inhibits the caffeine-induced release. However, dantrolene alone did not antagonize the HgC12-induced inhibition. 3. Since caffeine depletes the intracellular Ca 2÷ stores of the smooth endoplasmic reticulum, HgC12 probably inhibits by binding to SH groups of 1Department of Oral Biology,Section of Physiology and Biochemistry,Dental Faculty, University of Oslo, 0316 Oslo, Norway. 2To whom correspondence should be addressed at Department of Oral Biology, P.O. Box 1052, Blindem, 0316 Osto, Norway. 623 0272-43401941120~0623507.0010 ~ 1994 Plenum Publishing Corporation