Differences in alkaline earth stimulation of neurotransmitter release from isolated brain synaptosomes

Summary

In the presence of 15 or 55 mM K⁺ buffer (calcium-deficient), pulses of the alkaline earths (Ca²⁺, Sr²⁺, Ba²⁺) stimulated secretion of previously accumulated [¹⁴C]GABA and [³H]norepinephrine (NE). For a 1 mM alkaline earth pulse in the presence of 15 mM K⁺, both GABA and NE release were ordered Ba²⁺>Sr²⁺>Ca²⁺. On the other hand, in 55 mM K⁺ the ordering was Ba²⁺>Sr²⁺∼Ca²⁺. The change in ordering resulted from an increase in Ca-dependent release at higher K⁺. In fact, Ba-dependent release was smaller in 55 mM K⁺ solution than in 15 mM K⁺ solution.

D-600 (10 μM), an antagonist of calcium influx, decreased both Ca- and Ba-dependent release of [¹⁴C]-GABA and [³H]NE in 15 mM K⁺ buffer. D-600 inhibited Ca-dependent release 60–70% whereas Ba-dependent release was inhibited only 30–45%.

A CaCl₂ (1 mM), BaCl₂ (1 mM) or KCl (30 mM) pulse in 15 mM K⁺ buffer increased both [¹⁴C]GABA and endogenous GABA release. The Ba²⁺ pulse released more [¹⁴C] and endogenous GABA than did the Ca²⁺ pulse. The 30 mM KCl pulse released less [¹⁴C] and endogenous GABA than did either the Ba²⁺ or the Ca²⁺ pulse. However, the specific activity of the K-induced release was significantly higher than the specific activity of either Ca- or Ba-dependent GABA release.

In substituting for Ca²⁺, Ba²⁺ may gain intracellular access to stimulus-secretion coupling processes via permeation at both Ca²⁺ and K⁺ ionophores.