RT Journal Article
SR Electronic
T1 The Synaptic Vesicle: Calcium Ion Binding to the Vesicle Membrane and Its Modification by Drug Action
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 778
OP 788
VO 12
IS 5
A1 E. K. MATTHEWS
A1 J. J. NORDMANN
YR 1976
UL http://molpharm.aspetjournals.org/content/12/5/778.abstract
AB The ionogenic nature of the synaptic vesicle surface and its calcium adsorption characteristics have been 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 µm sec-1 cm V-1, corresponding to a surface ζ 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, markedly decreased the surface charge. From the monomolecular adsorption isotherm the number of Ca2+ binding sites was found to be 4.17 x 1012 cm-2, with an electrochemical free energy of calcium ion adsorption, ΔGCa2+, of -5.00 kcal mole-1, increasing to -5.64 kcal mole-1 at low (0.02) ionic strength. Adenine and pyridine nucleotides (1 mM) were without effect on synaptic vesicle mobility. In contrast, 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 neunotransmitter release process. ACKNOWLEDGMENTS We are indebted to Dr. P. M. Dean and Mrs. G. A. Currell for their expert help in this study.