Calcium channel a2d protein (CaVa2d1) is the drug target for gabapentin and pregabalin for analgesia, epilepsy and anxiety. a2d protein also interacts directly with thrombospondin1 and thrombospondin4 secreted from astrocytes to stabilize synapses.
That is really interesting - any hypothesis about what they might be doing? In a recent study on astrocyte control of capillary blood flow in the cortex (in rats), I identified phospholipase D2, phospholipase A2, cycloxygenase and prostaglandin E synthase to be expresssed in astrocyte endfeet along capillaries (http://www.nature.com/neuro/journal/v19/n12/full/nn.4428.html). I was only looking for enzymes related to arachidonic acid synthesis or metabolism and never looked for any channels. I wonder whether these CaVa2d1 might play a role in astrocyte-pericyte signalling for neurovascular control or blood brain barrier maintenance.
However, I took a look at the Barres transcriptome and that shows that CaVa2d1 is most highly expressed by neurons, followed by OPCs and only then in astrocytes. Do you think this is because it is only expressed in the endfeet and not throughout the cell body/processes perhaps?
The material I have does not distinguish neurons from astrocytes (peroxidase staining with non-fluorescent light microscopy). I strongly suspect that the a2d protein is in neuronal cells that are very close to astroctye endfeet. However, I am interested in glial proteins that might interact with neuronal a2d in the extracellular space. THANKS for your reply.
Dear Charles,
Interesting finding. Since you have used peroxidase staining (DAB?) and that you are at U of M (Go Blue!), it might be interesting to prepare some new material for electron microscopy. Are there antibodies that recognize an intracellular portion of the channel that you could use, in addition to what you are already using?
I don't have time to search to see if retinal ganglion cells express this particular channel, particularly in optic axons. If they don't, the optic nerve might be a good place to look for expression (or not) in astrocytes, since the nerve only has axons in addition to different types of glial cells. Their morphology is fairly well characterized.
Just some thoughts,
Jill
Just from scanning published literature, I found the following proteins studied in astrocyte endfeet that appear to have extracellular domains:
Thrombospondin-1, CD31, aquaporin-4, integrin a1b1, potassium channels Kir4.1 and BK
Is anyone familiar with other proteins localized there?
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