Divergent expression of delayed rectifier K+ channel subunits during mouseheart development

The repolarization phase of the cardiac action potential is dependent on tr ansmembrane K+ currents. The Slow (,K,) and fast (,K,) components of the de layed-rectifier cardiac K+ current are generated by pore-forming a subunits KCNQ1 and KCNH2, respectively, in association with regulatory beta -subuni t KCNE1, KCNE2 and perphaps KCNE3. In the present study we have investigate d the distribution of transcripts encoding these five potassium channel-for ming subunits during mouse heart development as well as the protein distrib ution of KCNQ1 and KCNH2. KCNQ1 and KCNH2 mRNAs (and protein) are first exp ressed at embryonic day (E) 9.5, showing comparable levels of expression wi thin the atrial and ventricular myocardium during the embryonic and fetal s tages. In contrast, the beta -subunits display a more dynamic pattern of ex pression during development. KCNE1 expression is first observed at E9.5 thr oughout the entire myocardium and progressively is confined to the ventricu lar myocardium. With further development (E16.5), KCNE1 expression is mainl y confined to the compact ventricular myocardium. KCNE2 is first expressed at E9.5 and it is restricted already to the atrial myocardium. KCNE3 is fir st expressed at E8.5 throughout the myocardium and with further development , it becomes restricted to the atrial myocardium. The fact that alpha subun its are homogeneously distributed within the myocardium, whereas the beta s ubunits display a regionalized expression profile during cardiac developmen t, suggest that differences in the slow and fast component of the delayed-r ectifier cardiac K+ currents between the atrial and the ventricular cardiom yocytes are mainly determined by differential beta -subunit distribution, ( C) 2001 Elsevier Science B.V. All rights reserved.