Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells.
Extracellular tau promotes an increase in the level of intracellular calcium in cultured neuronal cells. We have found that such increase is impaired in the presence of antagonists of muscarinic receptors. In order to identify the nature of those receptors, we have tested the effect of different specific muscarinic receptor antagonists on tau promoted calcium increase. Our results indicate that the increase does not take place in the presence of antagonists of muscarinic (mainly M1 and M3) receptors. A similar increase in intracellular calcium was found in non-neuronal cells transfected with cDNA of M1 and M3 muscarinic receptors when tau was added. These results suggest that observed effect of tau protein on neuronal (neuroblastoma and primary cultures of hippocampal and cortical neurons) cells is through M1 and M3 muscarinic receptors. Therefore blocking M1 and for M3 receptors, by using specific receptor antagonists, can prevent that tau toxic effect that could take place in tauopathies.
Gómez-Ramos
A
A
Centro de Biología Molecular Severo Ochoa, C/Nicolás Cabrera no 1, Campus de Cantoblanco, 28049, Madrid, Spain.
Díaz-Hernández
M
M
Rubio
A
A
Miras-Portugal
M T
MT
Avila
J
J
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D002522:Chlorocebus aethiops; D045604:Extracellular Fluid / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D043643:Receptor, Muscarinic M1 / Q000502:physiology*; D043587:Receptor, Muscarinic M3 / Q000502:physiology*; D016875:tau Proteins / Q000502:physiology*
D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D016875:tau Proteins; D002118:Calcium