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1 Department of Pharmacology and Toxicology, Dresden University of Technology, Fetscherstr. 74, Dresden, 01307 Germany
Dipeptidyl-aminopeptidase-like protein 6 (DPPX) was recently shown in the brain to modulate the kinetics of transient A-type currents by accelerating inactivation and recovery from inactivation. Since the kinetics of human cardiac transient outward current (Ito) are not mimicked by coexpression of the 
-subunit Kv4.3 with its known ß-subunit KChIP2, we have tested the hypothesis that DPPX may serve as an additional ß-subunit in the human heart. With quantitative real-time RT-PCR strong mRNA expression of DPPX was detected in human ventricles and was verified at the protein level in human but not in rat heart by a DPPX-specific antibody. Co-expression of DPPX with Kv4.3 in Chinese hamster ovary cells produced Ito-like currents, but compared with expression of KChIP2a and Kv4.3, the time constant of inactivation was faster, the potential of half-maximum steady-state inactivation was more negative and recovery from inactivation was delayed. Co-expression of DPPX in addition to Kv4.3 and KChIP2a produced similar current kinetics as in human ventricular myocytes. We therefore propose that DPPX is an essential component of the native cardiac Ito channel complex in human heart.
(Received 29 March 2005;
accepted after revision 5 May 2005;
first published online 12 May 2005)
Corresponding author E. Wettwer: Department of Pharmacology and Toxicology, Medical Faculty, Dresden University of Technology, Fetscherstr. 74, 01307 Dresden, Germany. Email: wettwer{at}rcs.urz.tu-dresden.de
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