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

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.

• Authors: Kosuke Ando, Yoshihisa Kudo, Kyota Aoyagi, Ryoki Ishikawa, Michihiro Igarashi, Masami Takahashi
• Journal: Brain research (Brain Res) Vol. 1535 Pg. 1-13 (Oct 16 2013) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 23973605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Calmodulin
• Myo5a protein, rat
• Sesterterpenes
• Glutamic Acid
• ophiobolin A
• Myosin Type V
• Myosin Heavy Chains

Topics

• Animals
• Calmodulin (metabolism)
• Cerebellum (cytology, drug effects, metabolism)
• Cerebral Cortex (cytology, drug effects, metabolism)
• Dose-Response Relationship, Drug
• Glutamic Acid (metabolism)
• Myosin Heavy Chains (metabolism)
• Myosin Type V (metabolism)
• Neurons (cytology, drug effects, metabolism)
• PC12 Cells
• Rats
• Sesterterpenes (pharmacology)
• Synaptic Transmission (drug effects, physiology)
• Synaptic Vesicles (drug effects, metabolism)