Reciprocal regulation of cardiac Na-K-ATPase and Na/Ca exchanger: hypertension, thyroid hormone, development. 1995

C E Magyar, and J Wang, and K K Azuma, and A A McDonough
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033, USA.

Inhibiting cardiac Na pump activity decreases the driving force for the Na/Ca exchanger transport that increases cellular Ca stores and contractility. Decreased abundance of Na pumps would be expected to have the same effect as decreased activity unless there was reciprocal regulation of Na/Ca exchanger expression to oppose the effects of depressed Na pump activity on intracellular Ca stores. The aim of this study was to test the hypothesis that cardiac Na/Ca exchanger abundance is regulated in a reciprocal fashion to Na-K-ATPase abundance in a number of models known to have altered Na-K-ATPase abundance. In renovascular hypertension, cardiac ventricular Na-K-ATPase alpha 1-levels are unaltered, alpha 2-isoform subunit mRNA and protein levels decrease to 0.76 +/- 0.06 and 0.56 +/- 0.07 of control, respectively, and the Na/Ca exchanger protein (not mRNA) increased 1.35 +/- 0.11-fold. In the transition from hypothyroid to hyperthyroid cardiac alpha 1 doubles, alpha 2-protein increases 8.83 +/- 1.06-fold, and the Na/Ca exchanger protein decreases to 0.64 +/- 0.11. A similar pattern was seen during cardiac development in the preweaning rat heart. Treatment with the antiarrhythymic amiodarone has no effect on alpha 1, decreases alpha 2-protein expression to 0.51 +/- 0.08 of control, and increases exchanger expression 1.42 +/- 0.16-fold. In conclusion, the reciprocal regulation of the Na/Ca exchanger and of Na-K-ATPase alpha 2-expression provides evidence for a homeostatic mechanism that would oppose the changes in cellular Ca stores driven by the changes in Na-K-ATPase activity.

UI MeSH Term Description Entries
D006978 Hypertension, Renovascular Hypertension due to RENAL ARTERY OBSTRUCTION or compression. Hypertension, Goldblatt,Goldblatt Syndrome,Goldblatt Hypertension,Renovascular Hypertension,Syndrome, Goldblatt
D008297 Male Males
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D000254 Sodium-Potassium-Exchanging ATPase An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients. ATPase, Sodium, Potassium,Adenosinetriphosphatase, Sodium, Potassium,Na(+)-K(+)-Exchanging ATPase,Na(+)-K(+)-Transporting ATPase,Potassium Pump,Sodium Pump,Sodium, Potassium ATPase,Sodium, Potassium Adenosinetriphosphatase,Sodium-Potassium Pump,Adenosine Triphosphatase, Sodium, Potassium,Na(+) K(+)-Transporting ATPase,Sodium, Potassium Adenosine Triphosphatase,ATPase Sodium, Potassium,ATPase, Sodium-Potassium-Exchanging,Adenosinetriphosphatase Sodium, Potassium,Pump, Potassium,Pump, Sodium,Pump, Sodium-Potassium,Sodium Potassium Exchanging ATPase,Sodium Potassium Pump
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging
D000638 Amiodarone An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. Amiobeta,Amiodarex,Amiodarona,Amiodarone Hydrochloride,Amiohexal,Aratac,Braxan,Corbionax,Cordarex,Cordarone,Kordaron,L-3428,Ortacrone,Rytmarone,SKF 33134-A,Tachydaron,Trangorex,Hydrochloride, Amiodarone,L 3428,L3428,SKF 33134 A,SKF 33134A
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
D000833 Animals, Suckling Young, unweaned mammals. Refers to nursing animals whether nourished by their biological mother, foster mother, or bottle fed. Animal, Suckling,Suckling Animal,Suckling Animals
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23

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