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Modulation of sodium channel gating by beta subunits and novel sodium channel blockers; Synaptic transmission in dorsal horn neurons
My research interests are divided into two main areas: 1)Modulation of sodium channel gating by beta subunits and novel sodium channel blockers. Sodium channels play a major role in the development of action potentials in excitable cells. Pharmacological modulation of sodium channel activity have proven extremely useful in the treatment of disorders such as epilepsy, pain and cardiac arrhythmias. Using cultured mammalian cells as expression systems, neuronal and cardiac sodium channels are studied using the patch clamp electrophysiology technique. Sodium currents are recorded and modulation of gating kinetics by auxiliary beta subunits determined. In collaboration with Dr. Milton Brown (Dept. of Chemisty) the potency of novel sodium channel blockers are also tested for sodium channel inhibition. The use of novel compounds allows the probing of the local anesthetic binding site with a view to developing more potent local anesthetics. 2) Synaptic transmission in dorsal horn neurons. Nociceptive transmission from the periphery is mediated by Ad and C fibres that terminate predominately on substantia gelatinosa neurons of laminae I and II of the dorsal horn. Using adult rat spinal cord slices these neurons are visualized using infra-red video microscopy and whole cell patch clamp electrophysiology used to record both excitatory and inhibitory synaptic transmission. Using a suction electrode, Ad and C fibres are stimulated and the post synaptic current recorded. Synaptic transmission under normal and condition of neuropathic pain are studied with a view to understanding the mechanisms of pain transmission. The effects of novel sodium channel blockers on synaptic transmission are also tested for the potential treatment of neuropathic pain.