The actions of presynaptic snake toxins on membrane currents of mouse motor nerve terminals.
1. The m. triangularis sterni of the mouse was used to investigate the actions of dendrotoxin, beta-bungarotoxin, crotoxin, taipoxin, bee venom phospholipase A2, aprotinin and apamin on presynaptic currents which flow inside the perineural sheath of nerve bundles upon nerve stimulation. 2. Neither the fast K+ current (IK,f) nor the Ca2+-dependent K+ current IK(Ca) (unmasked after blockade of IK,f by 3,4-diaminopyridine) was affected by the neurotoxins and drugs mentioned. 3. Inhibition of both IK,f and IK(Ca) by tetraethylammonium (30 mM) prolonged presynaptic depolarization owing to Ca2+ influx through fast and slow Ca2+ channels. Additional application of dendrotoxin, beta-bungarotoxin, crotoxin or taipoxin in the nanomolar range caused further prolongation of Ca2+ influx, presumably due to blockade of slowly activating K+ current (IK,s). Onset of toxin effects was immediate and could not be reversed by washing for 60 min. 4. Similar prolongation of slow Ca2+ current was effected by 3,4-diaminopyridine, whereas addition of apamin, aprotinin or phospholipase A2 left the signals unchanged. 5. These data indicate that facilitatory actions of dendrotoxin, beta-bungarotoxin, taipoxin and crotoxin are mediated by an increase of Ca2+ entry into nerve terminals. The actions of these toxins are discussed in terms of a blockade of presynaptic K+ channels with slow activation kinetics.
D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000200:Action Potentials / Q000187:drug effects; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D007611:Aprotinin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology*; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D011188:Potassium / Q000502:physiology; D012910:Snake Venoms / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000631:Aminopyridines; D007473:Ion Channels; D012910:Snake Venoms; D013757:Tetraethylammonium Compounds; D001030:Apamin; D019789:Tetraethylammonium; D007611:Aprotinin; D015761:4-Aminopyridine; D010741:Phospholipases A; D054467:Phospholipases A2; D000077770:Amifampridine; D011188:Potassium; D002118:Calcium