Calcium uptake of rat brain synaptosomes as a function of membrane potential under different depolarizing conditions.
The uptake of 45Ca2+ was measured in brain synaptosomes under conditions designed to depolarize the membranes. Membrane potential was estimated from the distribution of 86Rb+ between the intra- and extracellular compartments. K+ depolarization (8-60 mM) only increased "a2+ uptake beyond a threshold depolarization of about 10 mV, whereas veratridine (5-40 microM) induced an increased Ca2+ uptake at a concentration which depolarized the membrane less than this threshold. Ouabain did not enhance Ca2+ uptake, but the depolarization it produced did not reach threshold. Ca2+ influx already stimulated by K+ depolarization can be further enhanced by veratridine without any parallel change in membrane potential. Only the pathway mediating Ca2+ uptake during K+ depolarization can be inactivated: Ca2+ uptake evoked by K+ depolarization is decreased in synaptosomes pre-depolarized in the presence of a high concentration of K+. In contrast, pre-depolarization does not change Ca2+ uptake evoked by veratridine. Ca2+ channel blockers, such as verapamil and diltiazem but not nifedipine, in concentrations of 10-100 microM, decrease the stimulation of Ca2+ uptake by high K+ concentration without influencing depolarization, whereas the effect of veratridine on Ca2+ uptake is only inhibited when its effect on Na+ channels is also prevented. It is concluded that Ca2+ uptake during K+ depolarization proceeds through voltage-dependent Ca2+ channels similar to those of squid axon, whereas veratridine activates an additional Ca2+ entry, possibly via influx through open Na+ channels. Different quantitative relationships are found between acetylcholine release of synaptosomes and the amount of Ca2+ taken up by different mechanisms: the same amount of Ca2+ uptake is accompanied by a greater increase of acetylcholine release if the uptake is induced by K+ depolarization rather than veratridine.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism*; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010042:Ouabain; D014701:Veratridine; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium