Developmental Evolution of the Delayed Rectifier Current IKs in Canine Heart Appears Dependent on the Β Subunit Mink

OBJECTIVES We tested the hypothesis that the developmental changes occurring in I-Kr and I-Ks can be explained by changes in the expression of ERG encoding I-Kr, and KCNQ1, the beta subunit minK, and the recently reported subunit FHL2 encoding I-Ks.BACKGROUND The delayed rectifier current contributes importantly to the developmental evolution of the canine myocardial action potential. Specifically, in left ventricular epicardial myocytes, I-Ks is absent and I-Kr is the major repolarizing current until age 4 weeks. With subsequent development, I-Ks density increases and I-Kr decreases, resulting in an altered voltage-time course of repolarization.METHODS We used Western blotting and real-time polymerase chain reaction to compare the expression of ERG, KCNQ1, minK, and FHL2 in 1-week-old pups and adult dogs. RESULTS ERG levels are high at I week and decrease significantly with age, consistent with developmental decrease in I-Kr Whereas expression of KCNQ1 and FHL2 is unchanged between the two age groups, minK is minimally expressed at I week and increases in adults, consistent with developmental increase in I-Ks.CONCLUSIONS A reduction in ERG explains the developmental decrease in I-Kr, whereas the accessory subunit minK appears to be the critical determinant of developmental evolution of I-Ks. (C) 2004 Heart Rhythm Society. All rights reserved.