Calcium uptake related to K+-depolarization and Na+/Ca2+ exchange in sheep brain synaptosomes

The uptake of Ca2+ by synaptosomes induced by K+-depolarization and by Na+/Ca2+ exchange was studied in synaptosomes in which the internal Na+ and K+ contents were varied by prolonged incubation at 30 degrees C or by inhibiting the Na+, K+-ATPase with 1 mM ouabain. Increased Na+ content of the synaptosomes is associated with an increase in Ca2+ uptake when the synaptosomes are placed in depolarizing K+ media. Furthermore, reduction in the [Na+]o, when the [K+]o is increased, in substitution for [Na+]o, to depolarize the membrane, further increases the Ca2+ uptake. Under these conditions, Ca2+ entry probably occurs through voltage-sensitive channels and through the Na+/Ca2+ exchanger. Destruction of the Na+ gradient by monensin, or preloading the synaptosomes with K+, completely inhibits the Ca2+ uptake in a K+-depolarizing medium. It is shown that if the Na+ gradient is maintained constant during K+-depolarization, the Ca2+ uptake is very low and that most of the Ca2+ uptake is correlated with the Na+ gradient. Evidence is presented that K+ may stimulate the Na+/Ca2+ exchange mechanism. Furthermore, divalent cations, Mg2+, Mn2+ and Zn2+, known to block Ca2+ channels, also inhibit Na+/Ca2+ exchange.