Biomaterial Database

Acute effects of thyroid hormone on inward rectifier potassium channel currents in guinea pig ventricular myocytes. 1996

Y Sakaguchi, and G Cui, and L Sen

Department of Medicine, Veterans Administration Medical Center, West Los Angeles, USA.

Thyroid hormones play an important role in cardiac electrophysiology. However, the regulation of cardiac ionic channels by thyroid hormones is still unclear. To evaluate the acute effect of 3,3',5-triiode-L-thyronine (T3) on inward rectifier potassium channel (IK1) action potentials, whole-cell IK1 currents and steady-state single IK1 currents were recorded in guinea pig ventricular myocytes. Acute exposure of cells to T3 resulted in shortening of the action potential durations. This effect was initiated at 5-15 min and reached a stable plateau at 25 min. The amplitude of steady-state whole-cell IK1 was significantly increased by T3 at 1 nM to 1 microM concentration rage and with ED50 12 nM/liter. T3 (1 microM) increased IK1 by 68 +/- 7% at -40 mV and 52 +/- 9% at -100 mV. Similar effects were observed with triiodothyroacetic acid, an analogue of T3 that does not stimulate DNA transcription. The single IK1 open probability (Po) was increased 7 +/- 1% by 1 nM T3 (n = 9, P < 0.05) and 42 +/- 6% by 1 microM T3 at -40 mV (n = 18, P < 0.0001). However, the channel unit amplitude, time constants of open and fast-closed time were not changed. T3 shortened interburst duration at each membrane potential but did not change the burst behavior. To elucidate detailed mechanism, we assumed a three-state model (C1 <==> C2 <==> O) and calculated each rate constant. T3 significantly increased the rate constant, k+1, for the transition from the C1 to the C2 state at RP -40 mV (2.84 +/- 0.56 to 7.28 +/- 1.23 sec-1, P < 0.01), RP -20 mV (3.63 +/- 0.95 to 10.17 +/- 2.60 sec-1, P < 0.05) and RP (6.73 +/- 1.20 to 21.94 +/- 4.49 sec-1, P < 0.01). However, the other rate constants were not affected. These results demonstrate that T3 enhances IK1 with the increment in Po, which mainly results from shortening of interburst duration without any changes in burst behavior. Hence, the shortening of interburst duration is due to acceleration of the transition from the C1 to the C2 state. The enhanced IK1 by T3 might be one of the causes for shortened action potential duration in hyperthyroidism.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011336	Probability	The study of chance processes or the relative frequency characterizing a chance process.	Probabilities
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D006352	Heart Ventricles	The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.	Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor