Knockout mice for pharmacological screening: testing the specificity of Na+-Ca2+ exchange inhibitors.
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.
Reuter
Hannes
H
Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, Calif 90095-1760, USA.
Henderson
Scott A
SA
Han
Tieyan
T
Matsuda
Toshio
T
Baba
Akemichi
A
Ross
Robert S
RS
Goldhaber
Joshua I
JI
Philipson
Kenneth D
KD
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D010647:Phenyl Ethers / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000235:genetics*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000814:Aniline Compounds; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D013890:Thiourea