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Brain Res. 2013 Oct 16;1535:1-13. doi: 10.1016/j.brainres.2013.08.018. Epub 2013 Aug 23.

Calmodulin-dependent regulation of neurotransmitter release differs in subsets of neuronal cells.

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1
School of Life Sciences, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Abstract

The purpose of this study was to determine whether calmodulin (CaM) plays a role in neurotransmitter release by examining the effect that ophiobolin A (OBA), a CaM antagonist, on neurotransmitter release from clonal rat pheochromocytoma PC12 cells, primary cortical neurons, and primary cerebellar granule cells. OBA inhibited Ca²⁺/CaM-dependent phosphorylation of cAMP response element binding protein in all cell types tested. Moreover, Ca²⁺-dependent release of dopamine and acetylcholine from PC12 cells were remarkably reduced by OBA in a dose-dependent and temporal manner, but neurotransmitter release partially recovered with the addition of CaM in membrane permeabilized PC12 cells. OBA and several synthetic CaM antagonists suppressed Ca²⁺-dependent glutamate release from cerebral cortical neurons, but not from cerebellar granule cells. Myosin Va, a CaM binding protein, localized to synaptic vesicles of PC12 cells and cerebral cortical neurons, but not in cerebellar granule cells. OBA suppressed Ca²⁺-induced myosin Va dissociation from secretory vesicles, and inhibited secretory vesicle motility in PC12 cells. These results suggest that CaM, although not essential, regulates neurotransmitter release in a subset of neurons and secretory cells, and myosin Va is a possible target of OBA in this process.

KEYWORDS:

ACh; BSA; CREB; CaM; Cerebellar granule cells; Cerebral cortical neurons; DA; DMEM; DNase; Dulbecco’s modified Eagle’s medium; Dulbecco’s phosphate buffered saline; FCS; Glu; HRP; MEM; Myosin Va; Neurotransmitter release; OBA; PAGE; PBS; PC12 cells; SDS; SNAP-25; SNARE; VAMP-2; acetylcholine; bovine serum albumin; cAMP response element binding protein; calmodulin; deoxyribonuclease; dopamine; fetal calf serum; glutamate; hGH; horseradish peroxidase; human growth hormone; minimum essential medium; ophiobolin A; polyacrylamide gel electrophoresis; sodium dodecyl sulphate; soluble N-ethylmaleimide-sensitive fusion protein receptor; synaptosomal-associated protein of 25kDa; vesicle-associated membrane protein-2

PMID:
23973605
DOI:
10.1016/j.brainres.2013.08.018
[Indexed for MEDLINE]
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