Characterisation of transient outward current in young human atrial myocytes

The aim was to characterise the development of the transient outward current (Ito) in atrial myocytes of infants and children.

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.

A transient inactivating current characteristic of Ito 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 Ito 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 Ito time course of inactivation showed an apparent maturational evolution, with the youngest infants having slightly but significantly slower inactivation kinetics. The kinetics of Ito recovery from inactivation were well described by a single exponential model with no appreciable developmental trend in time course.

Ito is expressed in human atrial myocytes from early infancy and does not show significant developmental changes in current density. The relative contribution of Ito 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 Ito inactivation but not in recovery from inactivation, perhaps excluding the latter as a mechanism for the previously reported functional unavailability of Ito in young human atrial muscle.