Intracellular Ca2+ stores modulate SOCCs and NMDA receptors via tyrosine kinases in rat hippocampal neurons

• Published in: Cell calcium (Edinburgh) 2009-07, Vol.46 (1), p.39-48
• Main Authors: Koss, David J, Riedel, Gernot, Platt, Bettina
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Boron Compounds - pharmacology; Calcium; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Calcium Signaling - drug effects; Culture; Genistein - pharmacology; Hippocampus; Hippocampus - enzymology; Hippocampus - metabolism; Homeostasis - drug effects; Kinases; Metabotropic glutamate receptors; N-Methylaspartate - pharmacology; Neurons - drug effects; Neurons - enzymology; Neurons - metabolism; Phosphatases; Phosphorylation; Potassium Chloride - pharmacology; Protein Tyrosine Phosphatases - metabolism; Protein-Tyrosine Kinases - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Store-operated calcium channel; Thapsigargin - pharmacology; Tyrosine; Vanadates - pharmacology
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2009.04.001

Abstract The regulation of intracellular Ca2+ signalling by phosphorylation processes remains poorly defined, particularly with regards to tyrosine phosphorylation. Evidence from non-excitable cells implicates tyrosine phosphorylation in the activation of so-called store-operated Ca2+ channels (SOCCs), but their involvement in neuronal Ca2+ signalling is still elusive. In the present study, we determined the role of protein tyrosine kinases (PTKs) and tyrosine phosphatases (PTPs) in the coupling between intracellular Ca2+ stores and SOCCs in neonatal rat hippocampal neurons by Fura-2 Ca2+ imaging. An early Ca2+ response from intracellular stores was triggered with thapsigargin, and followed by a secondary plasma membrane Ca2+ response. This phase was blocked by the non-specific Ca2+ channel blocker NiCl and the SOCC blocker, 2-aminoethoxydiphenyl borate (2-APB). Interestingly, two structurally distinct PTK inhibitors, genistein and AG126, also inhibited this secondary response. Application of the PTP inhibitor sodium orthovanadate (OV) also activated a sustained and tyrosine kinase dependent Ca2+ response, blocked by NiCl and 2-APB. In addition, OV resulted in a Ca2+ store dependent enhancement of NMDA responses, corresponding to, and occluding the signalling pathway for group I metabotropic glutamate receptors (mGluRs). This study provides first evidence for tyrosine based phospho-regulation of SOCCs and NMDA signalling in neurons.