Polyamine FTX-3.3 and Polyamine Amide sFTX-3.3 Inhibit Presynaptic Calcium Currents and Acetylcholine Release at Mouse Motor Nerve Terminals

Abstract

FTX-3.3 is the proposed structure of a calcium-channel blocking toxin that has been isolated from the funnel web spider ( Agelenopsis aperta). The effects of FTX-3.3 and one of its analogues, sFTX-3.3, on acetylcholine release, on presynaptic currents at mouse motor nerve terminals and on whole-cell sodium currents in SK.N.SH cells (a human neuroblastoma cell line) have been studied. FTX-3.3 (10–30 μM) and sFTX-3.3 (100–300 μM) reversibly reduced release of acetylcholine by approximately 70–90% and 40–60%, respectively. FTX-3.3 (10 μM) blocked the fast component of presynaptic calcium currents by approximately 60%. sFTX-3.3 (100 μM) reduced the duration of the slow component of presynaptic calcium currents by about 50% of the control and also reduced presynaptic sodium current by approximately 20% of the control. sFTX-3.3 (100 μM) reduced whole-cell sodium current recorded from SK.N.SH cells by approximately 15%, whereas FTX-3.3, even at 200 μM, did not affect this current. Since the only difference in chemical structures of these toxins is that sFTX-3.3 has an amide function which is absent in FTX-3.3, the amide function may be responsible for the reduced potency and selectivity of sFTX-3.3. This study also provides further support for the existence of P-type calcium channels at mouse motor nerve terminals. © 1997 Elsevier Science Ltd. All rights reserved.