Ca2+ signals:
Molecular Mechanisms and Integrative Functions Collaborative Research Center 894

Project A14 - Andreas Beck & Veit Flockerzi

TRPC channels in micro- and macroglial cells

Glial cells shape neuronal excitability and synaptic transmission, and numerous studies implicate transient receptor potential C (TRPC) channels as coordinators of Ca2+ and Na+ signaling in these cells. However, the poor quality of available antibodies and the lack of appropriate controls including cells from TRPC-deficient mice are constraints, which limit essentially the strength of those studies. We have identified TRPC3 gene expression in cortical astrocytes, the dependence of Ca2+ signals in these cells on the presence of functional TRPC3 channels, and an essential contribution of TRPC3 to glial cell migration and to brain injury-induced astrogliosis.

We, now, are planning

1) to apply transcriptional profiling and antibody-based affinity purification to identify expression of additional TRPC genes and proteins in mouse cortex-derived astrocytes and microglial cells,

2) to study TRPC3 activation and signaling in astrocytes utilizing gain-of-function TRPC3 mutant and TRPC3 gene-deficient mice as controls, and to extend these studies to other TRPCs and microglial cells, depending on the results of aim 1. Starting with cultured cortex-derived primary glial cells we

3) will extend these studies to glial cells from other regions of the brain and to astrocytes in situ, and include studies on the impact of TRPC channels for integrative functions of glial cells such as glial responses to brain injury.