THE PREJUNCTIONAL INHIBITORY EFFECT OF SURAMIN ON NEUROMUSCULAR-TRANSMISSION IN-VITRO

The P-2 purinoceptor antagonist suramin reverses skeletal muscle paral ysis evoked by non-depolarizing neuromuscular blocking agents in vitro and in vivo. To further study the action of suramin on neuromuscular transmission, (miniature) endplate potentials ((m.)e.p.ps), motor nerv e terminal currents and the release of radiolabeled acetylcholine was measured in isolated nerve-muscle preparations. In preparations paraly sed by low Ca2+/high Mg2+ conditions, suramin (10 mu M-1 mM) induced a concentration-dependent decrease in quantal content of the e.p.ps wit hout affecting m.e.p.ps. Suramin reversed neuromuscular block by d-tub ocurarine in these preparations. In erabutoxin paralysed preparations, suramin (40 mu M-1 mM) inhibited the motornerve terminal currents rel ated to Ca2+ influx concentration-dependently, but did not affect Nacurrents. Suramin-induced inhibition of Ca2+ currents was not antagoni zed by ATP gamma S. Suramin (300 mu M) reduced [C-14]acetylcholine out flow in non-paralysed rat phrenic nerve-hemidiaphragm preparations by 32%. As suramin did not chelate Ca2+, these results indicate that sura min inhibits neuromuscular transmission by blocking prejunctional Ca2 channels, thereby decreasing acetylcholine release upon nerve stimula tion.