Developmental Changes in Action Potential and Membrane Currents in Fetal, Neonatal and Adult Guinea-pig Ventricular Myocytes

Abstract

Developmental changes in electrophysiological properties were investigated in enzymatically isolated ventricular cardiomyocytes from fetal (45–55 days after conception), neonatal (1–5 days after birth) and adult (45–60 days after birth) guinea-pigs. Action potentials were elicited at 1 Hz in current-clamp mode, and membrane currents were measured using whole cell voltage clamp method. Action potential durations at 50% and 90% repolarization decreased between fetal and neonatal periods and increased between neonatal and adult periods, while there was no substantial age-related change in resting membrane potential and action potential overshoot. Because cell membrane capacitance increased with age, indicating a developmental increase in cell size, current density was normalized to membrane capacitance for each cell. The l-type calcium current (l CaL) density at 0 and +10 mV was significantly smaller in fetal and neonatal cells than in adult ones, although the voltage dependence and inactivation kinetics were similar among the three age groups. The delayed rectifier K +current (l K) density at 0 and +30 mV was significantly smaller in fetal cells than in neonatal and adult ones. No significant difference in the inward rectifier K +current (l K1) density was observed among the three age groups. Thus, the electrophysiological properties of the guinea-pig ventricular myocytes were demonstrated to change during pre- and postnatal development. The observed changes in action potential duration could be explained by changes in the balance between l Kand l CaL.