Ligands for Stretch Activated Ion Channels.
STATE UNIV OF NEW YORK AT BUFFALO AMHERST
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During tenure of the grant we have made tremendous strides in finding active ligands for the mechanosensitive channels. We developed a simple screen for the toxins based upon hypotonic swelling of GH3 clonal neurons which produced increases in internal Ca2 levels that could be measured using Fura-2. Addition of active venoms would lead to a decrease in Ca2 levels following swelling. Screening a variety of spider and scorpion venoms, we found that none of the scorpions tested 12 but one of the 8 spiders tested was able to block volume activated Ca2 uptake. The raw venom also blocked stretch activated ion channels in Xenopus oocytes, chick heart cells and GH3 cells, and whole cell mechanical currents in chick heart cells.