Abstract
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. Agentswith a broader action that includes Ca2+ channel blockmay 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.
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Sipido, K., Varro, A., Eisner, D. (2006). Sodium Calcium Exchange as a Target for Antiarrhythmic Therapy. In: Basis and Treatment of Cardiac Arrhythmias. Handbook of Experimental Pharmacology, vol 171. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29715-4_6
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