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

Abstract

SUMMARY1. In ventricular muscle of rat heart, the action potential undergoes a major dlevelopmental 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 v-entricles of rats aged 1-10 days. All recordings were made at 22-23 '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' m) which preferentially blocks voltage-activated transient outward currents affected action potentials at all ages, but increases in duration were m(ist 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' m, a blocker of inwardly rectifying potassium channels, had a marked slowing effect on repolarization in all the three age groups. Resting rnembrane depolarization was also produced by barium.

Prenatal Exposure to Carbon Monoxide Affects Postnatal Cellular Electrophysiological Maturation of the Rat Heart

“…I to channel density increases steeply from birth to 1 month of life in the rat, as shown by our data (Table 3) and in agreement with the literature. 15,16 At variance with I to , we found that I Ca,L density is not affected by postnatal growth (Table 2), because it remains unaltered during development, as reported by Katsube et al 22 and in contrast to Gomez et al 21 Hormonal systems play a major role in controlling the maturation of rat cardiac myocyte functional properties. Importantly, the densities of I to and I Ca,L are regulated by thyroid hormones in the rat cardiac ventricle.…”

“…It is apparent that at 2 weeks after birth, the AP profile from Ctr is nearly identical to that recorded from CO-exposed rats (A). The AP duration (APD), as expected, 15,16 is quite long; in these cells, the phase of rapid repolarization appears to be slowed down, and the plateau phase is long. With development (4 weeks old), the AP from Ctr myocytes shows the expected decrease in duration and a prominent rapid repolarization phase; conversely, the AP from CO myocytes remains long (B).…”

“…Importantly, the densities of I to and I Ca,L are regulated by thyroid hormones in the rat cardiac ventricle. 16,18,26 Moreover, postnatal evolution of sympathetic innervation parallels ventricular APD shortening in the rat and contributes to the developmental differences in I to . 27 Likewise, an abnormal sympathetic innervation in neonatal rats prolongs the ECG QT interval, 17 which is an indicator of a prolonged ventricular myocyte repolarization.…”

“…9 -12 In newborns, the QT interval temporarily lengthens and then physiologically shortens during the first 6 months of life. 13 Postnatal electrophysiological remodeling has been documented for both newborn dogs 14 and rats 15,16 : Ventricular repolarization spontaneously undergoes a progressive shortening during the first weeks of life. Neurohumoral and hormonal signals (sympathetic innervation, thyroid hormone) seem to play a key role in these developmental changes, because their deficiency causes an abnormally prolonged repolarization.…”

Transient outward potassium current and Ca2+ homeostasis in the heart: beyond the action potential

“…In neonatal rodent ventricle, I to,f and I to,s (whose density is paralleled by Kv4.2/4.3 and Kv1.4 expression, respectively) show similar contributions to total I to, while in adults the former contributes over 90% (2,11,27,28). In the neonatal myocardium, the AP is longer than in the adult, and AP shortening with maturation coincides with an increase in myocardial I to density and channel isoform switch (28).…”