Developmental changes in action potential and membrane currents in fetal, neonatal and adult guinea-pig ventricular...

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 (lCaL) 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 (lK) 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 (lK1) 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 lK and lCaL.