Effects of ?-latrotoxin, lanthanides and elevated potassium concentration on acetylcholine release and free intracellular calcium levels in rat cerebral cortex synaptosomes.
At peripheral cholinergic nerve terminals, lanthanum (La(3+)) increases acetylcholine (ACh) release and supports transmitter release induced by ?-latrotoxin (?-LTx). The present experiments investigate these interactions at central cholinergic nerve terminals by measuring the effects of La(3+) and gadolinium (Gd(3+)), another element of the lathanide (Ln(3+)) series, on ACh release and free intracellular calcium concentrations ([Ca(2+)](i)) in rat cortical synaptosomal preparations. Ln(3+) had no measurable effect on basal synaptosomal ACh release, ACh contents or [Ca(2+)](i). Release of ACh induced by ?-LTx was inhibited by the presence of Ln(3+), as were ACh release responses to elevated K(+). The rise in [Ca(2+)](i) induced by ?-LTx was inhibited by Ln(3+) at concentrations similar to those that inhibited ACh release. Addition of Ln(3+) subsequent to an ?-LTx-evoked increase in [Ca(2+)](i) resulted in an immediate (within 4 s) cessation of calcium entry. Gd(3+) binding studies using the radioisotope (153)Gd(3+) revealed that Gd(3+) bound extremely rapidly to synaptosomes and that under the experimental conditions used to measure either ?-LTx- or K(+)-induced ACh release, little or no free Gd(3+) was likely to exist in the medium. We conclude that at central cholinergic neurons 1-Ln(3+) do not affect basal ACh release and 2-Ln(3+) are effective inhibitors for ?-LTx-induced ACh release and changes in [Ca(2+)](i).
Scheer
H W
HW
Department of Pharmacology, University of Montreal, Montreal, Quebec Canada.
Rosenthal
L P
LP
Collier
B
B