Circulation Research. 2001;88:864-876
doi: 10.1161/hh0901.090298
doi: 10.1161/hh0901.090298
© 2001 American Heart Association, Inc.
Review |
Cardiac Na+-Ca2+ Exchange
Molecular and Pharmacological Aspects
From the Department of Molecular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Correspondence to Munekazu Shigekawa, MD, PhD, Department of Molecular Physiology, National Cardiovascular Center Research Institute, Fujishiro-dai 5-7, Suita, Osaka 565-8565, Japan. E-mail shigekaw{at}ri.ncvc.go.jp
Abstract—The
Na+-Ca2+
exchanger (NCX) is one of the essential regulators of
Ca2+ 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 
-1 and -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)phenyl]ethyl]isothiourea
methanesulfonate (KB-R7943), appears to exhibit unique selectivity for
Ca2+-influx–mode NCX activity. Data
obtained with these inhibitors should provide a basis for
designing more selective and clinically useful drugs targeting
NCX.
Key Words: Na+-Ca2+ exchange • Ca2+ transport • cardiac muscle • excitation-contraction coupling
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