Sodium calcium exchange as a target for antiarrhythmic therapy.
In search of better antiarrhythmic therapy, targeting the Na/Ca exchanger is an option to be explored. The rationale is that increased activity of the Na/Ca exchanger has been implicated in arrhythmogenesis in a number of conditions. The evidence is strong for triggered arrhythmias related to Ca2+ overload, due to increased Na+ load or during adrenergic stimulation; the Na/Ca exchanger may be important in triggered arrhythmias in heart failure and in atrial fibrillation. There is also evidence for a less direct role of the Na/Ca exchanger in contributing to remodelling processes. In this chapter, we review this evidence and discuss the consequences of inhibition of Na/Ca exchange in the perspective of its physiological role in Ca2+ homeostasis. We summarize the current data on the use of available blockers of Na/Ca exchange and propose a framework for further study and development of such drugs. Very selective agents have great potential as tools for further study of the role the Na/Ca exchanger plays in arrhythmogenesis. For therapy, they may have their specific indications, but they carry the risk of increasing Ca2+ load of the cell. Agents with a broader action that includes Ca2+ channel block may have advantages in other conditions, e.g. with Ca2+ overload. Additional actions such as block of K+ channels, which may be unwanted in e.g. heart failure, may be used to advantage as well.
Sipido
K R
KR
'Lab. of Experimental Cardiology, KUL, Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium. Karin.Sipido@med.kuleuven.ac.be
Varro
A
A
Eisner
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D
D000200:Action Potentials / Q000187:drug effects; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000150:complications; D006321:Heart / Q000502:physiology; D006333:Heart Failure / Q000150:complications; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D010647:Phenyl Ethers / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000502:physiology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000814:Aniline Compounds; D000889:Anti-Arrhythmia Agents; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D013890:Thiourea; D002118:Calcium