Thyroid hormone regulates postnatal expression of transient K⁺ channel isoforms in rat ventricle

1. The ability of thyroid hormone to regulate the postnatal changes of the Ca²⁺-independent transient outward K⁺ current (I(t)) was studied in rat ventricular myocytes. 2. In rat ventricle, I(t) is very small at birth and then increases markedly between postnatal days 8 and 20. The time course of this increase in current density is similar to that of a significant rise in plasma thyroid hormone (T₃) levels. 3. During early development, the density of expression of I(t) can be altered by changes in thyroid hormone levels. Eight days after birth the density of I(t) measured at +50 mV in control animals is 2.2 ± 0.4 pA pF^-1. This value is about 3-fold larger (6.5 ± 0.8 pA pF^-1) in myocytes from age-matched hyperthyroid animals. When the plasma T₃ level in newborn rats is not allowed to increase, or is decreased by making animals hypothyroid, this age dependent increase in I(t) fails to occur. 4. Using RNase protection assays, K(v)4.2 and K(v)4.3 mRNA levels were measured in ventricular tissues obtained from age-matched 8-day-old control and hyperthyroid rats. In hyperthyroid animals, where an approximately 3-fold increase in I(t) was identified, increases in the mRNA levels for K(v)4.2 and K(v)4.3 were 1.6-fold and 2.6-fold, respectively. 5. These results show that thyroid hormone can regulate the development of I(t) in rat ventricle. Direct measurements of I(t) density and mRNA levels as a function of development and thyroid hormone levels also strongly suggest that the K(v)4.2 and K(v)4.3 channels are essential components of I(t) in rat ventricular cells.