Presynaptic calcium signals and transmitter release are modulated by calcium-activated potassium channels.
The regulation of synaptic transmission by Ca(2+)-activated potassium (gKca) channels was investigated at the frog neuromuscular junction (nmj). Charybdotoxin (CTX), a blocker of certain types of gKca channels, induced a twofold increase of transmitter release. Similar results were obtained with purified natural toxin, synthetic toxin, and recombinant toxin. Apamin, a blocker of a different type of gKca channel, did not alter transmitter release. CTX was ineffective after intraterminal Ca2+ buffering was increased by application of the membrane-permeant Ca2+ buffer dimethyl-BAPTA-AM. By itself, the permeant buffer first caused a slight increase in transmitter release before release was eventually decreased. This increase of release did not occur when the buffer was applied in the presence of CTX or Ba2+, another gKca channel blocker. Stimulus-evoked entry of Ca2+ in nerve terminals, detected with the fluorescent Ca2+ indicator FLUO-3, was increased after blockade of gKca channels by CTX. CTX had no effect on the amount or the time course of synaptic depression. The results are consistent with the hypothesis that CTX-sensitive gKca channels normally narrow the presynaptic action potential and thus, by indirectly regulating Ca2+ entry, can serve as powerful modulators of evoked transmitter release. In order to affect presynaptic action potentials, the gKca channels must be located close to Ca2+ channels.
Department of Physiology, University of Toronto, Ontario, Canada.
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Robitaille
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Charlton
D000200:Action Potentials; D000814:Aniline Compounds; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002021:Buffers; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D018999:Charybdotoxin; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D011894:Rana pipiens; D011994:Recombinant Proteins / Q000494:pharmacology; D012604:Scorpion Venoms / Q000494:pharmacology; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D014966:Xanthenes
D000814:Aniline Compounds; D002021:Buffers; D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D015221:Potassium Channels; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D014966:Xanthenes; D018999:Charybdotoxin; C059715:Fluo-3; D001030:Apamin; D002118:Calcium