Laboratory of Experimental Neurophysiology
PI: Cornelia Poulopoulou PhD
The research in our lab is concentrated in two main areas
On one hand we study the expression and functional characteristics of ion channels expressed in lymphocytes freshly isolated from peripheral blood of patients with CNS and autoimmune disorders with special interest on the voltage-gated potassium channel Kv1.3, that is known to act as the molecular switch that drives lymphocytes in their activated state, and the single channel characteristics of the ionotropic glutamate-gated channels (NMDA, AMPA and kainite).
The other area of interest in the lab is the regulation of human lymphocyte physiology by transmitters present in the plasma (glutamate, Achetylcholine, dopamine) that we typically think to function in the CNS but as shown by many labs including ours, their receptors are expressed and reused in the immune cells of the peripheral blood.
Like in the CNS much of the regulation by transmitters is mediated through the electrical properties of the cell. In our laboratory we use the patch clamp technique as our primary read out to examine how transmitters may regulate the electrical properties of these cells both at rest and during activation by immune stimuli or mitogens.
Our lab was the first to identify the Kv1.3 channel as one of the target molecules through which the neurotransmitter glutamate exerts both its enhancing and suppressing effects on T-lymphocyte activation by demonstrating that glutamate at doses below normal plasma levels enhances Kv1.3 channel activity while at doses above normal levels inhibits the activity of the channel. Furthermore we showed that Kv1.3 modulation by glutamate is mediated through the activation of group I and group II cognate metabotropic glutamate receptors (mGluRs).
The expression and function of the metabotropic glutamate receptors has been investigated in T-cells from peripheral blood of patients with neurodegenerative (Alzheimer and Amyotrophic Lateral Sclerosis) and system and CNS autoimmune diseases (Systemic lupus erythromatose (SLE) and Multiple Sclerosis (MS)).
A new area of interest in our lab is the expression of synaptic proteins in the immune cells of the peripheral blood of both healthy individuals and patients with CNS disorders such as autism.
The research projects that are running in the lab are
1. Investigation of the Kv1.3 channel activity in T-cells isolated from peripheral blood of Multiple sclerosis patients (in collaboration with Prof. George Chandy Departments of Physiology and Biophysics, Neurology, and Microbiology and Molecular Genetics, School of Medicine, University of California Irvine)
2. Study of the mechanism of immunosuppressive action of high doses of glutamate.
3. Characterization of functional characteristics of the kainate receptors in T-lymphocytes of healthy individuals and the effects of their activation in lymphocyte physiology (in collaboration with Prof. Linda Nowak Cornell University Department of Molecular Medicine Ithaca NY)
4. Investigation of the expression of synaptic proteins in T-lymphocytes isolated by healthy individuals and patients with autism spectrum disorders (in collaboration with the A’ Psychiatric department Athens University)
5. Study of the mechanism of α7 nicotinic receptor (α7nAChR) immunoreactivity in lymphocytes (in collaboration with Prof. Roger Papke University of Florida, Gainesville Department of Pharmacology and Therapeutics).
6. Study of the expression levels of the mGluR 2, 3 and 4 in lymphocytes isolated from patients with Multiple Sclerosis
The main techniques employed in our lab are tissue culture, patch-clamp electrophysiology, RNA isolation and PCR as well as immunocytochemistry and western blot.
Collaborators
Markakis Ioannis MD PhD, Director of the Neurology Clinic in Nikaia General Hospital
Florakis Andreas MD PhD, Psychiatric Clinic at Thriasion Hospital
Graduate Students
Master Thesis Students
Charitakis Ioannis BS
Spanou Syrago BS
Doctorate candidates
Elpida Repousi MD
Penelope Galani BS Msc