Transient outward current in young and adult diseased human atria

In human atrial fibers, the action potential undergoes a major developmental change in shape in the months immediately after birth. Transient potassium outward currents, which may affect the shape of the action potential, have been studied using a whole cell voltage-clamp technique with single cells from the atria of young patients aged 3-60 mo. Transient outward current (I(to)) amplitude was measured as the difference between the peak current and the steady-state outward current (I(late)) at the end of the voltage step. The density of I(to) was significantly reduced in adult diseased cells (n = 18) compared with normal cells (n = 21) in a large range of potential and absent in young diseased cells (n = 13). Furthermore, the I(late) recorded in young cells was significantly greater (23.7 +/- 5.74 pA/pF at 60 mV) than in adult normal cells (12.71 +/- 2.25 pA/pF at 60 mV), whereas I(late) was not significantly different between both groups of adult cells. Nevertheless, a 4-aminopyridine-sensitive I(to) has been recorded in young cells. A decrease in the frequency of clamp steps (from 0.1 to 0.01 Hz) did not reactivate a I(to) in young cells. This absence of 4-aminopyridine-sensitive Ito in young cells probably results from either a normal developmental change of this current or from pathological alterations like those described in adult diseased atria.