Polyamine FTX-3.3 and polyamine amide sFTX-3.3 inhibit presynaptic calcium currents and acetylcholine release at mouse motor nerve terminals.
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 microM) and sFTX-3.3 (100-300 microM) reversibly reduced release of acetylcholine by approximately 70-90% and 40-60%, respectively. FTX-3.3 (10 microM) blocked the fast component of presynaptic calcium currents by approximately 60%. sFTX-3.3 (100 microM) 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 microM) reduced whole-cell sodium current recorded from SK.N.SH cells by approximately 15%, whereas FTX-3.3, even at 200 microM, 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.
Fatehi
M
M
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, UK.
Rowan
E G
EG
Harvey
A L
AL
Moya
E
E
Blagbrough
I S
IS
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000494:pharmacology*; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; C102391:FTX 3.3; D011073:Polyamines; D017661:Receptors, Presynaptic; D015222:Sodium Channels; C102392:sFTX 3.3; D000109:Acetylcholine