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 (It) was studied in rat ventricular myocytes. 2. In rat ventricle, It 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 It can be altered by changes in thyroid hormone levels. Eight days after birth the density of It 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 It fails to occur. 4. Using RNase protection assays, Kv4.2 and Kv4.3 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 It was identified, increases in the mRNA levels for Kv4.2 and Kv4.3 were 1.6-fold and 2.6-fold, respectively. 5. These results show that thyroid hormone can regulate the development of It in rat ventricle. Direct measurements of It density and mRNA levels as a function of development and thyroid hormone levels also strongly suggest that the Kv4.2 and Kv4.3 channels are essential components of It in rat ventricular cells.
Shimoni
Y
Y
Department of Physiology, University of Calgary School of Medicine, Alberta, Canada.
Fiset
C
C
Clark
R B
RB
Dixon
J E
JE
McKinnon
D
D
Giles
W R
WR
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000254:growth & development / Q000502:physiology* / Q000503:physiopathology; D006352:Heart Ventricles; D006980:Hyperthyroidism / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels; D013961:Thyroid Gland / Q000502:physiology*; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000494:pharmacology
C497020:Kcnd2 protein, rat; C497023:Kcnd3 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D014284:Triiodothyronine; D002118:Calcium