Neuropathological effect of Delta mutation in SCCMS: Screening of open channel blockers as therapeutic agents
This project is mainly focused on delta mutation δS268F due to its diversity out of 12 various known mutations in 2 different ways. Significant successive reduction of their end plate potentials in spite of absence of endplate myopathy unlike other mutations, which is the slow channel pathological signature. Unaccounted distinct clinical behavior and abnormal electrophysiological abnormality and unrecognized mechanisms lead us to focus on novel delta mutations to unravel the mystery. in addition, unlike other SCCMS this delta mutation accquires slower opening rate along with sharing the property of delayed receptor closure rate. previous electrophysiological data earlier from our lab in recombinant homologous mouse δS268F nicotinic AChR expressed in Xenopus oocytes revealed the reduction in the Miniature End Plate Potentials(MEPPs) and significant reduction in amplitudes of MEPC, which supported the hypothesis. we want to take this project a step farther in estimating neuropathological effect of novel delta mutation in mice followed by various drug screening by long lived open-channel blockers of AChR that shorten the channel opening durations in estimating their clinical efficiency and efficacy for the betterment of the human race. We expect that these drugs either individually or in combined with affect the neuromuscular pathology by correcting the receptor kinetic abnormalitie