Associate Professor
Department of Physiology and Biophysics
UCD at Fitzsimons
RC-1 North Tower, P18-7121. PO Box 6511, Mail Stop F8307. Tel (303) 724-4531. Fax (303) 724-4501.
Email sukumar.v@uchsc.edu

Sukumar's Curriculum vitae

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SUMMARY

We are interested in understanding how a group of membrane proteins called ligand-gated ion channels modulate neuronal excitability in the central nervous system (CNS). Current research in the laboratory focuses on one member of this group, the nicotinic acetylcholine receptor (AChR). Though it is believed that alterations of AChR functions can have profound behavioral effects, the role that these receptors play in normal and abnormal functions of the CNS is largely unknown. Using a multidisciplinary approach involving biochemistry, molecular biology, electrophysiology, and calcium imaging, we are tracking the signaling pathways triggered by the activation of a subclass of AChRs that bind the snake venom toxin, alpha bungarotoxin (aBgt-AChRs). These receptors are highly permeable to calcium, an ion known to be an important second messenger for neurons. We use cultured neurons and slices from the rat hippocampus, an area of the brain involved in certain kinds of learning and memory and where these receptors are abundant as illustrated in this image (the fluorescent AChRs are superimposed on a brightfield image; the cell is about 25 micrometers in diameter). Cultured neurons serve as a model system to trace the consequences of receptor-induced calcium increases. One such effect, for example, could be the activation of the enzyme calcium/calmodulin-dependent protein kinase. If this is true, we would then determine the kinetics and spatial changes in calcium concentration necessary to activate this enzyme, the changes in gene expression caused by the triggering of this pathway and the consequences of this enzyme activation for ion channel functions on the neuron (See the FIGURE).

Using information about aBgt-AChR function obtained at the cellular level we are examining the role of these receptors in long-term plasticity of hippocampal synapses. The overall aim is to understand signal transduction by AChR channels and their role in mediating and modulating CNS functions. Another important consequence of this work will be to obtain stringent mechanistic correlates that explain the various actions of nicotine on the CNS.

 

• Sharma, G., and Vijayaraghavan, S. (2001). Nicotinic cholinergic signaling in hippocampal astrocytes involves calcium-induced calcium release from intracellular stores. Proc. Natl. Acad. Sci. 98:4148-4153.
  
• Berger, F., Gage, F.H., and Vijayaraghavan, S. (1998). Nicotinic Receptor-Induced Apoptotic Cell Death of Hippocampal Progenitor Cells. J. Neurosci. 18(17):6871-6881.
  
• Vijayaraghavan, S., Huang, B., Blumenthal, E.W., and Berg, D.K. (1995). Arachidonic acid as a possible negative feedback regulator of neuronal acetylcholine receptor function. J. Neurosci 15, 3679-3687.
  
• Vijayaraghavan, S. (1994). Science for art's sake. Nature 372, 590. Zhang, Z-w., Vijayaraghavan,S., and Berg, D.K. (1994). Neuronal acetylcholine receptors that bind a-bungarotoxin with high affinity function as ligand-gated ion channels. Neuron 12, 167-177.
  
• Vijayaraghavan, S., Pugh, P.C., Zhang, Z-w., Rathouz, M.M., and Berg, D.K. (1992). Nicotinic receptors that bind a-bungarotoxin on neurons raise intracellular free Ca++. Neuron 8, 353-362.
  
• Vijayaraghavan, S., Schmid, H.A., Halvorsen, S.W., and Berg, D.K. (1990). Cyclic AMP dependent phosphorylation of a neuronal nicotinic acetylcholine receptor a-type subunit. J. Neurosci. 10, 3255-3262.