RUTHENIUM RED, A NOVEL ENHANCER OF K-NERVE TERMINALS( CURRENTS AT MOUSE MOTOR)

The effects of ruthenium red (RR) on transmitter release and pre-synap tic currents were studied in the mouse neuromuscular junction. The act ion of RR (10 mu M) was shown not only in the complete suppression of nerve-evoked muscle contractions associated with the-depression of end plate potential amplitudes but also in the partial inhibition of the a mplitude of miniature-endplate potentials. However, the other rutheniu m compounds, ruthenium chloride and tris (2,2-bipyridyl) ruthenium chl oride did not significantly affect the neuromuscular transmission. In pre-synaptic waveform studies, the fast K+-current [IK(f)] as well as the Ca2+-activated K+-current [IK(ca)] was significantly enhanced by 1 0 mu M RR. Furthermore, 10 mu M RR antagonized the action of beta-bung arotoxin (a blocker of slow K+-channel [IK(s)] in enhancing pre-synapt ic Ca2+ currents. In contrast, the typical Ca2+-channel blockers, omeg a-agatoxin (0.5 mu M), Gd3+ (0.5 mM) and Cd2+ (0.3 mM) all suppressed the IK(ca). Although RR (1-30 mu M) inhibited the Ca2+-currents of the nerve terminals induced by the combined treatment with the K+-channel blockers, 3,4-diaminopyridine plus tetraethylammonium chloride in a c oncentration-dependent manner, it is considered that RR-enhanced K+ cu rrents were responsible for, at least in part, the observed inhibition of the Ca2+-current which led to the blockade of transmitter release. Copyright (C) 1996 Elsevier Science Ltd