H. Reuter, S. Henderson, T. Han, T. Matsuda, A. Baba, R. Ross, J. Goldhaber, K. Philipson
{"title":"Knockout Mice for Pharmacological Screening: Testing the Specificity of Na+-Ca2+ Exchange Inhibitors","authors":"H. Reuter, S. Henderson, T. Han, T. Matsuda, A. Baba, R. Ross, J. Goldhaber, K. Philipson","doi":"10.1161/01.RES.0000027529.37429.38","DOIUrl":null,"url":null,"abstract":"The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to electrically stimulated heart tubes from control mouse embryos or embryos with the Na+-Ca2+ exchanger knocked out. We monitored effects of the drugs on Ca2+ transients. Both drugs depress the Ca2+ transients at low concentrations even in the absence of any Na+-Ca2+ exchanger. KB-R7943 and SEA0400 are not completely specific and should be used with caution as Na+-Ca2+ exchange inhibitors.","PeriodicalId":10314,"journal":{"name":"Circulation Research: Journal of the American Heart Association","volume":"32 1","pages":"90-92"},"PeriodicalIF":0.0000,"publicationDate":"2002-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"146","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation Research: Journal of the American Heart Association","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1161/01.RES.0000027529.37429.38","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 146
Abstract
The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to electrically stimulated heart tubes from control mouse embryos or embryos with the Na+-Ca2+ exchanger knocked out. We monitored effects of the drugs on Ca2+ transients. Both drugs depress the Ca2+ transients at low concentrations even in the absence of any Na+-Ca2+ exchanger. KB-R7943 and SEA0400 are not completely specific and should be used with caution as Na+-Ca2+ exchange inhibitors.