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Effects of Monensin and Veratridine on Acetylcholine Release and Cytosolic Free Ca 2+ Levels in Cerebrocortical Synaptosomes of Rats
Author(s) -
Satoh Eiki,
Nakazato Yoshikazu
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08289.x
Subject(s) - veratridine , acetylcholine , synaptosome , monensin , chemistry , cytosol , synaptic vesicle , biophysics , endocrinology , biochemistry , biology , sodium , vesicle , membrane , organic chemistry , sodium channel , enzyme
Monensin (10 −8 ‐10 −4 M ) caused a dose‐dependent increase in the release of [ 3 H] acetylcholine ([ 3 H] ACh) from purified rat cerebrocortical synaptosomes, with an EC 50 of ∼1.6 × 10 −6 M . Extracellular Na + , but not Ca 2+ , was required for a monensin‐induced increase in the release of [ 3 H] ACh. Monensin also increased the cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) and uptake of 22 Na + in a dose‐dependent manner. Monensin continued to cause a dose‐dependent increase in [Ca 2+ ] i in the absence of extracellular Ca 2+ , although an ∼50% reduction was noted at concentrations of >10 −5 M. The EC 50 for the monensin‐induced increase in [Ca 2+ ] i was similar to that noted in the release of [ 3 H]ACh. Veratridine exhibited effects similar to those of monensin, but a large portion of the increase in [Ca 2+ ] i and [ 3 H] ACh release was dependent on extracellular Ca 2+ . Measurements of rhodamine 6G fluorescence indicated that monensin and veratridine caused synaptosomal hyperpolarization and depolarization, respectively. Tetrodotoxin (10 −6 M ) completely blocked all the effects of veratridine but had no effect on the activity of monensin. These results suggest that monensin increases the release of ACh at least in part by increasing [Ca 2+ ] i , resulting from the increase in the Na + influx through tetrodotoxin‐insensitive mechanisms in rat cerebrocortical synaptosomes.