Office: (317)-278-9342  
E-Mail:  trcummin@iupui.edu
 

My main interest is the biophysics of ion channels and the role of ion channels in neurological diseases. Sodium channel mutations have been linked to several neurological disorders including skeletal muscle non-distrophic myotonias, episodic ataxia and epilepsy. We have shown that mutations in the human skeletal muscle sodium channel, for example, play a crucial role in the development of hyperkalemic periodic paralysis. Changes in the expression and properties of voltage-gated sodium channels are also thought to play important roles in chronic pain. My lab uses electrophysiological, molecular biological and computer modeling techniques to study how specific voltage-gated sodium channels contribute to excitability and to neurological diseases. The long-term goals of my research are to develop a better understanding of the roles that ion channels in play in pathophysiological conditions and to develop strategies for the treatment of neurological disorders that involve ion channels.

Current work in my laboratory is focused on:

A) Understanding the role of peripheral neuronal sodium channels in nociception and neuropathic pain. Specific sodium channels are predominantly expressed in nociceptive sensory neurons. My lab is examining how the activity of these sodium channels are affected by inflammatory mediators and neurotrophins.

B) Investigating the role of sodium channels in genetic diseases. Sodium channel mutations have been identified in patients with epilepsy and skeletal muscle diseases. My lab characterizes the functional consequences of the different disease mutations in heterologous expression systems using patch-clamp techniques. We are also examining the effects of these mutant sodium channels on excitability in neurons and muscle cells.

C) Molecular pharmacology of voltage-gated sodium channels. Several projects focus on understanding the sensitivity of sodium channels to specific pharmacologic agents. Identify local anesthetics and anticonvulsants that preferentially target sodium channels involved in pain sensations. Identify the molecular determinants of sodium channel sensitivity to pore blockers. Identify biological toxins from marine cone snail and tarantula venoms that specifically target voltage-gated sodium channels. These studies will provide information on the pharmacology of specific voltage-gated sodium channels that are thought to play important roles in epilepsy and pain and hopefully will contribute to the development of better treatments for these neurological disorders.

Publications:

Herzog RI, Liu C, Waxman SG and Cummins TR. Calmodulin binds to the C-terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties. J. Neuroscience 23:8261-8270, 2003.

Cummins TR, Dib-Hajj SD, Waxman SG and Donnelly DF. Characterization and developmental changes of Na+ currents of petrosal neurons with projections to the carotid body. J. Neurophysiology 88: 2993-3002, 2002.

Cummins TR, Aglieco F, and Dib-Hajj SD. Critical molecular determinants of voltage-gated sodium channel sensitivity to m-conotoxins GIIIA/B. Molecular Pharmacology 61:1192-1201, 2002.

Bendahhou S, Cummins TR, Griggs RC and Ptácek LJ. Sodium channel inactivation defects as a mechanism for acetazolamide-exacerbated hypokalemic periodic paralysis. Annals Neurology 50:417-420, 2001.


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