{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:03:20Z","timestamp":1791216200699,"version":"4.1.0"},"update-to":[{"DOI":"10.1085\/jgp.117.4.371","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2000,5,1]],"date-time":"2000-05-01T00:00:00Z","timestamp":957139200000}}],"reference-count":58,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,5,1]]},"abstract":"<jats:p>We have identified a 35 amino acid peptide toxin of the inhibitor cysteine knot family that blocks cationic stretch-activated ion channels. The toxin, denoted GsMTx-4, was isolated from the venom of the spider Grammostola spatulata and has &amp;lt;50% homology to other neuroactive peptides. It was isolated by fractionating whole venom using reverse phase HPLC, and then assaying fractions on stretch-activated channels (SACs) in outside-out patches from adult rat astrocytes. Although the channel gating kinetics were different between cell-attached and outside-out patches, the properties associated with the channel pore, such as selectivity for alkali cations, conductance (\u223c45 pS at \u2212100 mV) and a mild rectification were unaffected by outside-out formation. GsMTx-4 produced a complete block of SACs in outside-out patches and appeared specific since it had no effect on whole-cell voltage-sensitive currents. The equilibrium dissociation constant of \u223c630 nM was calculated from the ratio of association and dissociation rate constants. In hypotonically swollen astrocytes, GsMTx-4 produces \u223c40% reduction in swelling-activated whole-cell current. Similarly, in isolated ventricular cells from a rabbit dilated cardiomyopathy model, GsMTx-4 produced a near complete block of the volume-sensitive cation-selective current, but did not affect the anion current. In the myopathic heart cells, where the swell-induced current is tonically active, GsMTx-4 also reduced the cell size. This is the first report of a peptide toxin that specifically blocks stretch-activated currents. The toxin affect on swelling-activated whole-cell currents implicates SACs in volume regulation.<\/jats:p>","DOI":"10.1085\/jgp.115.5.583","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:50:20Z","timestamp":1027702220000},"page":"583-598","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":322,"title":["Identification of a Peptide Toxin from<i>Grammostola spatulata<\/i>Spider Venom That Blocks Cation-Selective Stretch-Activated Channels"],"prefix":"10.1085","volume":"115","author":[{"given":"Thomas M.","family":"Suchyna","sequence":"first","affiliation":[{"name":"aFrom the Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice H.","family":"Johnson","sequence":"additional","affiliation":[{"name":"bNPS Pharmaceuticals, Inc., Salt Lake City, Utah 84108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Hamer","sequence":"additional","affiliation":[{"name":"bNPS Pharmaceuticals, Inc., Salt Lake City, Utah 84108"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph F.","family":"Leykam","sequence":"additional","affiliation":[{"name":"dDepartment of Biochemistry, Michigan State University\u2013National Institutes of Health Mass Spectrometry Facility, Michigan State University, East Lansing, Michigan 48824-1319"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas A.","family":"Gage","sequence":"additional","affiliation":[{"name":"dDepartment of Biochemistry, Michigan State University\u2013National Institutes of Health Mass Spectrometry Facility, Michigan State University, East Lansing, Michigan 48824-1319"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry F.","family":"Clemo","sequence":"additional","affiliation":[{"name":"cDepartment of Internal Medicine and Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive M.","family":"Baumgarten","sequence":"additional","affiliation":[{"name":"cDepartment of Internal Medicine and Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Sachs","sequence":"additional","affiliation":[{"name":"aFrom the Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,5,1]]},"reference":[{"key":"2023072520262404400_Bakhramovetal1995","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1113\/expphysiol.1995.sp003854","article-title":"Chloride current activated by hypotonicity in cultured human astrocytoma cells","volume":"80","author":"Bakhramov","year":"1995","journal-title":"Exp. 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