Calmodulin-dependent regulation of neurotransmitter release differs in subsets of neuronal cells
Autor: | Michihiro Igarashi, Kosuke Ando, Masami Takahashi, Ryoki Ishikawa, Kyota Aoyagi, Yoshihisa Kudo |
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Rok vydání: | 2013 |
Předmět: |
medicine.medical_specialty
Cerebellum Sesterterpenes Calmodulin Myosin Type V Glutamic Acid Biology PC12 Cells Synaptic Transmission Synaptic vesicle chemistry.chemical_compound Internal medicine Myosin medicine Animals Neurotransmitter Molecular Biology Cerebral Cortex Neurons Dose-Response Relationship Drug Myosin Heavy Chains General Neuroscience Glutamate receptor Rats Cell biology Endocrinology medicine.anatomical_structure nervous system chemistry biology.protein Synaptic Vesicles Neurology (clinical) Neuron Acetylcholine Developmental Biology medicine.drug |
Zdroj: | Brain Research. 1535:1-13 |
ISSN: | 0006-8993 |
Popis: | 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. |
Databáze: | OpenAIRE |
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