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Changes in thyroid state affect pHi and Nai+ homeostasis in rat ventricular myocytes
B M Wolska1, V Averyhart-Fullard, A Omachi
1Dept of Physiology and Biophysics, College of Medicine, Chicago, IL 60612-7342, USA.
Journal of Molecular and Cellular Cardiology
|November 5, 1997
Summary
Thyroid state impacts heart function by altering intracellular calcium (Ca2+) handling and myofilament responsiveness. Hyperthyroidism decreases intracellular pH (pHi) and increases intracellular sodium (Nai+), affecting cardiac contractility.
Area of Science:
- Cardiology
- Endocrinology
- Cell Physiology
Background:
- Thyroid hormones significantly influence cardiovascular function.
- Previous research focused on thyroid hormone effects on intracellular calcium (Ca2+) handling.
- The role of intracellular pH (pHi) and intracellular sodium (Nai+) in mediating these effects remained unclear.
Purpose of the Study:
- To investigate the hypothesis that thyroid state influences cellular Ca2+ flow and myofilament response to Ca2+ via alterations in pHi and Nai+.
- To elucidate the mechanisms by which thyroid status affects cardiac contractility at the cellular and organ levels.
Main Methods:
- Isolation of single cardiac myocytes from hypothyroid, euthyroid, and hyperthyroid rats.
- Loading myocytes with fluorescent probes for intracellular Ca2+ (fura-2/AM), pHi (BCECF/AM), and Nai+ (SBFI/AM).
- Measurement of myocyte shortening, contraction time, and fluorescence ratios.
- Utilizing Nuclear Magnetic Resonance (NMR) to assess pHi in Langendorff-perfused rat hearts.
- Analyzing mRNA expression levels of ion transporters (Na+/Ca2+ exchanger, Na+/H+ antiporter, Na+ channels).
Main Results:
- Hyperthyroid myocytes exhibited increased shortening extent and faster contraction times compared to hypothyroid myocytes.
- Hyperthyroidism led to increased peak Ca2+ amplitude, decreased pHi (by 0.19 pH units), and increased Nai+ (by 2.88 mM).
- Hyperthyroid hearts showed lower pHi (more acidic) than hypothyroid hearts.
- mRNA analysis revealed increased Na+/Ca2+ exchanger and Na+/H+ antiporter expression, and decreased Na+ channel expression in hyperthyroidism.
Conclusions:
- Altered thyroid state affects cardiac contractility through mechanisms involving changes in intracellular Ca2+ handling.
- Changes in pHi and Nai+ play a crucial role in modulating the myofilament response to Ca2+ under different thyroid states.
- The observed alterations in ion transporter gene expression contribute to the altered pHi and Nai+ levels in hyperthyroidism.
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