P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses.
We have studied the effect of the purified toxin from the funnel-web spider venom (FTX) and its synthetic analog (sFTX) on transmitter release and presynaptic currents at the mouse neuromuscular junction. FTX specifically blocks the omega-conotoxin- and dihydropyridine-insensitive P-type voltage-dependent Ca2+ channel (VDCC) in cerebellar Purkinje cells. Mammalian neuromuscular transmission, which is insensitive to N- or L-type Ca2+ channel blockers, was effectively abolished by FTX and sFTX. These substances blocked the muscle contraction and the neurotransmitter release evoked by nerve stimulation. Moreover, presynaptic Ca2+ currents recorded extracellularly from the interior of the perineural sheaths of nerves innervating the mouse levator auris muscle were specifically blocked by both natural toxin and synthetic analogue. In a parallel set of experiments, K(+)-induced Ca45 uptake by brain synaptosomes was also shown to be blocked or greatly diminished by FTX and sFTX. These results indicate that the predominant VDCC in the motor nerve terminals, and possibly in a significant percentage of brain synapses, is the P-type channel.
Instituto de Biologia Celular Facultad de Medicina, Universidad de Buenos Aires, Argentina.
O D
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Uchitel
D A
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Protti
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Sanchez
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Cherksey
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Sugimori
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Llinás
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010791:Phrenic Nerve / Q000502:physiology; D011073:Polyamines / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011689:Purkinje Cells / Q000502:physiology; D013095:Spermidine / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; C071920:FTX, spider toxin; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D010456:Peptides, Cyclic; D011073:Polyamines; D020960:omega-Conotoxins; D002104:Cadmium; C053423:Conus magus toxin; C038806:1,4-dihydropyridine; D001120:Arginine; D008274:Magnesium; D011188:Potassium; D002118:Calcium; D013095:Spermidine