Ca(2+)-dependent inactivation of P-type calcium channels in nerve terminals.
Rapid Ca2+ signals evoked by K+ depolarization of rat cerebral cortical synaptosomes were measured by dual-channel Ca2+ spectrofluorometry coupled to a stopped-flow device. Kinetic analysis of the signal rise phase at various extracellular Ca2+ concentrations revealed that the responsible voltage-dependent Ca2+ channels, previously identified as P-type Ca2+ channels, inactivate owing to the rise in intracellular Ca2+ levels. At millimolar extracellular Ca2+ concentrations the channels were inactivated very rapidly and the rate was dependent on the high influx rate of Ca2+, thus limiting the Ca2+ signal amplitudes to 500-600 nM. A slower, probably voltage-dependent regulation appears to be effective at lower Ca2+ influx rates, leading to submaximal Ca2+ signal amplitudes. The functional feedback regulation of calcium channels via a sensor for intracellular Ca2+ levels appears to be responsible for the different inhibition characteristics of Cd2+ versus omega-agatoxin IVa.
Tareilus
E
E
Institute of Zoophysiology, University Stuttgart-Hohenheim, Germany.
Schoch
J
J
Breer
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D009411:Nerve Endings / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013050:Spectrometry, Fluorescence / Q000379:methods
D015220:Calcium Channels; D002118:Calcium