Recent advances in cardiac NCX research highlight structural features of the ion translocation pathway and new classes of selective inhibitors like KB-R7943 targeting Ca2+-influx-mode NCX activity.
The Na(+)-Ca(2+) exchanger (NCX) is one of the essential regulators of Ca(2+) homeostasis in cardiomyocytes and thus an important modulator of the cardiac contractile function. The purpose of this review is to survey recent advances in cardiac NCX research, with particular emphasis on molecular and pharmacological aspects. The NCX function is thought to be regulated by a variety of cellular factors. However, data obtained by use of different experimental systems often appear to be in conflict. Where possible, we endeavor to provide a rational interpretation of such data. We also provide a summary of current work relating to the structure and function of the cardiac NCX. Recent molecular studies of the NCX protein are beginning to shed light on structural features of the ion translocation pathway in the NCX membrane domain, which seems likely to be formed, at least partly, by the phylogenetically conserved alpha-1 and alpha-2 repeat structures and their neighboring membrane-spanning segments. Finally, we discuss new classes of NCX inhibitors with improved selectivity. One of these, 2-2-[4-(4-nitrobenzyloxy)phenylethyl]isothiourea methanesulfonate (KB-R7943), appears to exhibit unique selectivity for Ca(2+)-influx-mode NCX activity. Data obtained with these inhibitors should provide a basis for designing more selective and clinically useful drugs targeting NCX.
Shigekawa et al. (Fri,) conducted a review in Cardiac contractile function and Ca2+ homeostasis. NCX inhibitors (e.g., KB-R7943) was evaluated. Recent advances in cardiac NCX research highlight structural features of the ion translocation pathway and new classes of selective inhibitors like KB-R7943 targeting Ca2+-influx-mode NCX activity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: