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 i n 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 (T-3) 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 T-3 level in n ewborn rats is not allowed to increase, or is decreased by making anim als 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 m easured in ventricular tissues obtained from age-matched 8-day-old con trol and hyperthyroid rats. In hyperthyroid animals, where an approxim ately 3-fold increase in I-t was identified, increases in the mRNA lev els 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 developmen t 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 s trongly suggest that the K(v)4.2 and K(v)4.3 channels are essential co mponents of I-t in rat ventricular cells.