Knockout Mice for Pharmacological Screening

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.