Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed after depolarization in canine heart.
The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37 degrees C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 microM SEA-0400 from 26.6+/-2.5 to 14.8+/-1.8 mV (n=9, P<0.05) and from 12.5+/-1.7 to 5.9+/-1.4 mV (n=3, P<0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.
Nagy
Zsolt A
ZA
Department of Pharmacology and Pharmacotherapy, Albert Szent-Györgyi Medical Center, Faculty of Medicine, University of Szeged, Dóm tér 12, PO Box 427, Szeged, Hungary.
Virág
László
L
Tóth
András
A
Biliczki
Péter
P
Acsai
Károly
K
Bányász
Tamás
T
Nánási
Péter
P
Papp
Julius Gy
JG
Varró
András
A
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000187:drug effects; D010647:Phenyl Ethers / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013328:Strophanthins / Q000494:pharmacology
D000814:Aniline Compounds; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D013328:Strophanthins; D002118:Calcium