Role of STIM1 in neuronal Ca2plus signaling and synaptic transmission

• Autorzy: Hartmann J. , Dijke A. , Konnerth A.
• Języki publikacji: EN

Abstrakty

EN

The metabotropic glutamate receptor type 1 (mGluR1) is highly expressed in cerebellar Purkinje cells (PCs). At parallel fiber-PC synapses, activation of mGluR1 evokes a complex synaptic response consisting of IP3 receptor-dependent Ca2+ release from endoplasmic reticulum (ER) Ca2+ stores and a slow depolarizing potential involving the transient receptor potential (TRPC) channel subunit TRPC3. We have shown recently that the ER Ca2+ sensor stromal interaction molecule 1 (STIM1) isimportant for cerebellar function by analyzing a PC-specific Stim1 knockout (STIM1pko) mouse line. Using wholecell recordings in combination with confocal Ca2+ imaging in acute cerebellar slices we demonstrated that STIM1 is a link of mGluR1 to its downstream effectors and regulates Ca2+ homeostasis in PCs (Hartmann et al. 2014, Neuron). In STIM1pko mice both TRPC3- mediated synaptic potentials and agonist-evoked inward currents were absent in PCs at resting membrane potential. Moreover, ER Ca2+ release was found to be strongly attenuated. However, activation of voltage-gated Ca2+ channels (VGCCs) transiently filled ER Ca2+ stores and rescued, for the filling period, TRPC3-mediated currents in the absence of STIM1. Next, we tested how TRPC3 gating depends on the filling state of ER Ca2+ stores. In control mice, we found that TRPC3-mediated currents are not altered when ER Ca2+ stores are emptied by blocking SERCA pumps using cyclopiazonic acid (CPA). Moreover, opening of VGCCs by short depolarizing pulsesin STIM1pko mice allows the transient activation of TRPC3 when store filling was prevented by the presence of CPA in the bath. Inclusion of 25 mM BAPTA into the pipette solution, however, in control mice strongly attenuates TRPC3-mediated currents and prevents their depolarization-evoked rescue in STIM1pko mice. Together, these results establish that STIM1 couples mGluR1 and TRPC3 in cerebellar PCs through the regulation of cytosolic rather than ER Ca2+ content.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S26-S27

Twórcy

autor

Hartmann J.

• Institute for Neuroscience, Technical University Munich, Munich, Germany
• Center for Integrated Protein Science Munich, Munich, Germany

autor

Dijke A.

• Institute for Neuroscience, Technical University Munich, Munich, Germany

autor

Konnerth A.

• Institute for Neuroscience, Technical University Munich, Munich, Germany
• Center for Integrated Protein Science Munich, Munich, Germany