The Use of Inhibitors of Mechanosensitive Ion Channels as Local Inhibitors of Peripheral Pain
Annual rept. 25 February 2013 - 24 February 2014
STATE UNIV OF NEW YORK AT BUFFALO AMHERST
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This is a basic research project designed to understand the role of mechanically sensitive excitatory ion channels MSC in the pathology of chronic pain, and the use of a small peptide inhibitor of these channels called GsMTx4 to treatment peripheral pain. The first aim of this project is to understand the mechanism of inhibition of a peptide inhibitor of caution selective mechanosensitive ion channels MSCs called GsMTx4 insertion depth in the mutagenisis. In aims 2 and 3 the goals are to understand the gating properties of MSC s, their sensitivity to inflammatory agents and their control by the cytoskeleton. We have shown that GsMTx4 insertion depth in the bilayer is an important factor affecting its inhibitory activity and that the positively charged amino acids are key to this attribute. We have identified that mutations to Piezo channels putative mechnoreceptors of DRGs that affect inactivation which is a key regulatory point for inflammatory agents. We have observed that the cytoskeleton of DRG s absorbs greater stress when treated with inflammatory agents and that filamin shows greater sensitivity than action.
- Anatomy and Physiology
- Medicine and Medical Research