A study of the developmental changes in outward currents of rat ventricular myocytes

1. In ventricular muscle of rat heart, the action potential undergoes a major developmental change in shape in the days and weeks immediately after birth. Potassium (K+) 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 ventricles of rats aged 1-10 days. All recordings were made at 22-23 degrees C. 2. Three discrete ages were chosen. 1-day (cells isolated within 24 h of birth), 5-day and 10-day rats. These parallel the developmental action potential shortening from neonatal towards adult type. Action potentials of single myocytes were initially of long duration at 1 day with a prominent plateau phase, but had shortened somewhat by 10 days of age. The 5-day group exhibited an action potential transitional in character between the earlier and later groups of cells. 3. Potassium current blocking agents were used to assess the importance of the various outward K+ currents for the action potential waveform at different ages. 4-Aminopyridine (4-AP; 2 x 10(-3) M) which preferentially blocks voltage-activated transient outward currents affected action potentials at all ages, but increases in duration were most pronounced in the 10-day group. Only a small prolongation of the initial phase of repolarization of 1-day action potentials was seen. Extracellular barium chloride, 0.1-2 x 10(-3) M, a blocker of inwardly rectifying potassium channels, had a marked slowing effect on repolarization in all the three age groups. Resting membrane depolarization was also produced by barium. 4. Developmental changes in the inwardly rectifying background current (IK1) and the cardiac transient outward current, It, were investigated. IK1 was recorded as the current sensitive to 2 x 10(-3) M-BaCl2 during voltage-clamp steps from a holding potential of -90 mV. It was found to decrease in magnitude, approximately by a factor of three, from 15 to 5 pA/pF during the first ten postnatal days. This reduction can explain the maturational slowing of repolarization during the final phase of the action potential in rat heart. 5. Current-voltage relations for IK1 from the three age groups crossed at the zero current potential at approximately -90 mV, near the calculated VK for the pipette filling solution and an external bath K+ concentration of 5 x 10(-3) M. This suggests that IK1 channels in these cells are quite selective for K+ ions and that developmental changes in the potassium selectivity are not responsible for changes in IK1.(ABSTRACT TRUNCATED AT 400 WORDS)