CHARACTERIZATION OF TRANSIENT OUTWARD CURRENT IN YOUNG HUMAN ATRIAL MYOCYTES

Objective: The aim was to characterise the development of the transient outward current (I-to) in atrial myocytes of infants and children. Methods: Whole cell voltage clamp was used to study outward currents in enzymatically isolated atrial myocytes from infants and children ranging in age from 3 days to 13.2 years. Results: A transient inactivating current characteristic of I-to was observed in 71 myocytes from 22 patients aged 3 days to 13.2 years, including a 10 day old infant born prematurely at 33 weeks gestation. There was no discernible developmental trend in I-to current density [10.74(SEM 0.65) pA.pF(-1) at +40 mV, n=71 cells from 22 patients] or voltage dependence of inactivation, newborn values being similar to those in older children, and in adults reported elsewhere. A developmental reduction in total outward current density was attributable entirely to diminution of the non-inactivating steady state current component. The I-to time course of inactivation showed an apparent maturational evolution, with the youngest infants having slightly but significantly slower inactivation kinetics. The kinetics of I-to recovery from inactivation were well described by a single exponential model with no appreciable developmental trend in time course. Conclusions: I-to is expressed in human atrial myocytes from early infancy and does not show significant developmental changes in current density. The relative contribution of I-to to myocyte repolarisation might increase with age as a result of diminution in the non-inactivating current component. There is an apparent slight maturational acceleration in the time course of I-to inactivation but not in recovery from inactivation, perhaps excluding the latter as a mechanism for the previously reported functional unavailability of I-to in young human atrial muscle.