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.

Background— Calcium-insensitive transient outward current ( I to ) is important to the development of cardiac memory (CM), which itself reflects the capacity of the heart to remodel electrophysiologically. We used cardiac pacing to test the hypothesis that CM evolution can be explained by developmental maturation of I to . Methods and Results— Acutely anesthetized dogs from 1 day old to adult were paced from the left ventricle (VP, n=29) or left atrial appendage (AP, n=12) to induce CM. T-wave vector displacement (TVD) obtained during VP was greater than with AP (adults, 0.39±0.06 mV; neonates, 0.04±0.01 mV; P <0.05). TVD began to increase at ≈40 days of age, reaching adult levels by ≈200 days. Microelectrode studies performed in 18 dogs (ages 3 to 94 days) after completing the CM protocol and 20 additional dogs (1 day old to adult) revealed that the epicardial action potential notch was absent in neonates, became apparent in the young, and was deepest in adults. The relationship between TVD and epicardial notch was such that as notch magnitude increased, TVD increased ( r =−0.65, P <0.05). KChIP2 and Kv4.3 mRNA (measured via reverse transcription–polymerase chain reaction) also increased with age. Conclusions— The inducibility of CM gradually increases with age in association with evolution of the epicardial action potential notch and mRNA expression for KChIP2 and Kv4.3. This suggests that the capacity of the heart to remodel electrophysiologically and to manifest memory during development depends in part on evolution of the determinants of I to .