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 Ca$^2+$ 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 Ca$^2+$
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 Ca$^2+$ load of the cell.
Agents with a broader action that includes Ca$^2+$ channel block
may have advantages in other conditions, e.g. with Ca$^2+$ 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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