Related Experiment Videos
Reciprocal regulation of cardiac Na-K-ATPase and Na/Ca exchanger: hypertension, thyroid hormone, development
C E Magyar1, J Wang, K K Azuma
1Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033, USA.
Abstract:
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.
Insights
Cardiac Na pump activity influences cellular calcium. This study found that the Na/Ca exchanger and Na-K-ATPase alpha 2-subunit are reciprocally regulated, suggesting a homeostatic mechanism to maintain calcium stores.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Biochemistry
Background:
- Cardiac Na pump (Na-K-ATPase) activity is crucial for regulating intracellular calcium via the Na/Ca exchanger.
- Altered Na-K-ATPase abundance may impact cellular calcium stores and cardiac contractility.
- Reciprocal regulation of these proteins could represent a homeostatic mechanism.
Purpose of the Study:
- To investigate the hypothesis that cardiac Na/Ca exchanger abundance is reciprocally regulated with Na-K-ATPase abundance.
- To examine this relationship in various models with altered Na-K-ATPase levels.
Main Methods:
- Quantitative analysis of Na-K-ATPase alpha 1 and alpha 2 subunit mRNA and protein levels.
- Measurement of Na/Ca exchanger protein and mRNA expression.
- Utilized models including renovascular hypertension, thyroid state transitions, cardiac development, and amiodarone treatment in rat hearts.
Main Results:
- In renovascular hypertension, Na-K-ATPase alpha 2 decreased while Na/Ca exchanger increased.
- In hyperthyroidism and cardiac development, Na-K-ATPase alpha 2 increased as Na/Ca exchanger decreased.
- Amiodarone treatment decreased Na-K-ATPase alpha 2 and increased Na/Ca exchanger.
Conclusions:
- Cardiac Na/Ca exchanger expression is reciprocally regulated with Na-K-ATPase alpha 2-subunit expression.
- This reciprocal regulation suggests a homeostatic mechanism to buffer changes in intracellular calcium stores.
- This finding has implications for understanding cardiac function and calcium handling in disease states.