Richard Miller, PhD Professor Molecular Pharmacology and Biological Chemistry Calcium channels in nerve communication and neurodegenerative disease Curricula: Neurobiology Pharmacology and Toxicology E-mail:   r-miller10@northwestern.edu

Our laboratory is interested in studying molecular aspects of nerve cell communication. One of our major interests has been to try and understand the structure and function of calcium channels. The influx of Ca into neurons through these channels is important for many reasons, including the release of neurotransmitters. We have identified a family of molecules that act as Ca channels in neurons and other types of cells. Each of these molecules has slightly different properties that underly different neuronal functions. We have analysed the properties of these molecules by examining their electrophysiological properties following their expression in heterologous expression systems and imaging techniques. Furthermore, we have generated calcium channel knockout mice that have interesting properties such as altered pain thressholds, seizures and memory defecits. We have also been interested in how Ca channels can be regulated by the activation of Gprotein coupled receptors. We have been analyzing the interaction of Gprotein subunits with Ca channels using FRET imaging and other techniques.

Other projects in our laboratory are aimed at understanding the molecular basis of neurodegenerative disease. We study Alzheimer's disease, Amyotrophic lateral sclerosis (Lou Gehrig's disease), HIV-1 related dementia and other neuropathological conditions. In the case of HIV-1 infection for example, we have been examining the properties and functions of HIV-1 receptors on neurons. These receptors are known to be receptors for chemokines -small proteins that are known to direct the functions of the immune system. We have shown that neurons express many types of chemokine receptors and that activation of these receptors can produce both short and long term effects on neurons. Activation of chemokine receptors expressed by sensory neurons produces neuronal excitation and pain. Activation of chemokine receptors on hippocampal neurons has a prosurvival effect, whereas binding of HIV-1 to these receptors induces apoptosis. We are studying the molecular mechanisms that produce this diverse effects with a view to understanding the molecular basis for HIV-1 related dementias.

Publications:

Simen, A.A. Lee, C.C., Simen, B.B., Bindokas, V.P., and Miller, R.J. (2001). The carboxy terminus of the Ca channel 1B subunit mediates selective inhibition by G-protein coupled receptors. J. Neurosci. 19, 7587-7597.

Oh, S.B., Tran, P.B., Gillard, S.E., Hurley, R.W., Hammond, D.L. and Miller, R.J. (2001). Chemokines and gp120 produce pain hypersensitivity by directly exciting polymodal nociceptors. J. Neurosci. 21, 5027-5035.

Miller, R.J., (2001). Rocking and Rolling with Calcium Channels. Trends in Neuroscience 24, 445-449.

View Publications by Richard Miller listed in the National Library of Medicine (PubMed).