The synaptic vesicle: calcium ion binding to the vesicle membrane and its modification by drug action
Matthews, E.K.; Nordmann, J.J.
Molecular Pharmacology 12(5): 778-788
1976
ISSN/ISBN: 0026-895X PMID: 995127 Document Number: 108587
The ionogenic nature of the synaptic vesicle surface and its Ca adsorption characteristics were investigated by microelectrophoretic measurements on vesicles isolated from the guinea pig cerebral cortex. The electrophoretic mobility of synaptic vesicles determined in 0.16 M KCl was -1.31 .mu.m s-1 cm V-1, corresponding to a surface .zeta. potential of -18.2 mV and surface charge density of 5451 esu cm-2. Whereas the monovalent cation species of the suspending medium had little effect upon the electrokinetic properties of synaptic vesicles, addition of Ca2+, 1-10 mM, decreased the surface charge. From the monomolecular adsorption isotherm the number of Ca2+ binding sites was 4.17 .times. 1012 cm-2, with an electrochemical free energy of Ca ion adsorption, .DELTA.GCa2+, of -5.00 kcal mol-1, increasing to 5.64 kcal mol-1 at low (0.02) ionic strength. Adenine and pyridine nucleotides (1 mM) were without effect on synaptic vesicle mobility. The neuroactive agents trifluoperazine, benzyl alcohol and amylobarbitone decreased the surface charge of the synaptic vesicle per se, irrespective of any effect on Ca2+ binding. These results are discussed in relation to the ionogenic properties of the synaptic vesicle surface and the molecular mechanism of drug action on the neurotransmitter release process.