Calcium transport in and out of brain nerve endings in vitro--the role of synaptosomal plasma membrane Ca2+-ATPase in Ca2+-extrusion.

The effects of cellular cations and ATP on calcium transport in and out of the nerve endings (synaptosomes) of mice brain were studied. The synaptosomes accumulated 45Ca time-dependently in the absence of ATP or other additions for at least 10 min. When ATP was present, the overall 45Ca accumulation was decreased and was maximal at about 4 min, after which it started to decline. Studies on the effects of cations with or without ATP at 4 min revealed selective activities for different cations. Mg2+ inhibited 45Ca accumulation in the absence of ATP but increased 45Ca accumulation when ATP was present. Similarly, ATP increased 45Ca accumulation only when Mg2+ was present. Na+, on the other hand, inhibited 45Ca accumulation both in the presence and absence of ATP and/or Mg2+. K+ increased 45Ca accumulation in the presence of ATP with or without Mg2+; however, K+-stimulation was not noted in the presence of 100 mM Na+, and in fact, K+ became inhibitory. The ATP-stimulated 45Ca accumulation in the presence of Mg2+ peaked within 4-6 min and then declined, suggesting release of 45Ca. Compatible with this notion, in 45Ca-loaded synaptosomes, ATP evoked 45Ca release which was accompanied by the appearance of Pi in the medium. Although ATP-activated 45Ca-release can occur in the presence of Mg2+, Mg2+ is not required and, in fact, is inhibitory. Rapid release of 45Ca was also noted when 45Ca-loaded synaptosomes were incubated in the presence of Na+ without ATP. It is concluded that Mg2+, Na+, K+ and ATP each has a specific role in regulating Ca2+ permeability of the plasma membrane, calcium binding and calcium extrusion.