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Normal responsiveness to external Ca and to Ca-channel modifying agents in hypertrophied rat heart
F Callens-el Amrani1, E Mayoux, C Mouas
1Institut National de la Santé et de Recherche Médicale (INSERM) U127, Hôpital, Paris, France.
Insights
Chronic pressure overload in rat hearts slows shortening velocity. This study found that calcium channel function remains normal, suggesting the issue lies within sarcomeres or sarcoplasmic reticulum, not calcium channels.
Area of Science:
- Cardiovascular Physiology
- Cardiac Hypertrophy Research
- Molecular Cardiology
Background:
- Chronic pressure overload in rat hearts leads to decreased maximum velocity of shortening.
- While an isomyosin shift contributes, changes in membrane proteins are also suspected.
- Inotropic responses to calcium channel modifiers and external calcium were investigated.
Purpose of the Study:
- To explore the role of membrane proteins, specifically calcium channels, in the reduced cardiac shortening velocity.
- To determine if alterations in calcium channel function contribute to impaired contractility in hypertrophied rat hearts.
Main Methods:
- Left ventricular hypertrophy was induced in rats via abdominal aortic stenosis.
- Isolated hearts were treated with calcium channel activator BAY K 8644 and nifedipine, as well as varying external calcium concentrations.
- Inotropic responses, measured by developed pressure and dP/dtmax, were assessed.
Main Results:
- The inotropic response to calcium channel modifiers and external calcium remained unchanged in hypertrophied hearts.
- This indicates that the total number of dihydropyridine binding sites and peak calcium current increase with hypertrophy.
- The observed slowing of velocity is not attributable to a reduced number of calcium channels.
Conclusions:
- The reduced maximum velocity of shortening in pressure-overloaded rat hearts is unlikely due to decreased calcium channel activity.
- Findings suggest that modifications within the sarcomeres or sarcoplasmic reticulum are more probable causes for the observed functional changes.
- This research highlights the importance of intracellular contractile machinery in cardiac adaptation to pressure overload.
Abstract:
In rat heart, the maximum velocity of shortening is decreased in response to chronic pressure overload. This is in part explained by an isomyosin shift, but several arguments suggest changes in membrane proteins. Inotropic response to calcium channel modifiers and to external calcium were simultaneously determined to explore this possibility. Left ventricular hypertrophy was induced by abdominal aortic stenosis and after 4-5 wk the left ventricular-to-body weight ratio increased by 61%. The effects of BAY K 8644 (10(-9) to 10(-6) M), a calcium channel activator, nifedipine (10(-9) to 10(-7) M), and external calcium (0.25-2.50 mM) were studied on isolated hearts at a coronary flow of 20 ml.min-1.g of left ventricle-1. The inotropic response (in percent changes in developed pressure and in dP/dtmax) was unmodified in the hypertrophied hearts. This work is in agreement with previous findings that both the total number of dihydropyridine binding sites and the peak magnitude of calcium current increase in proportion to the degree of hypertrophy. It suggests that the slowing of velocity could not be explained by a decreased number of Ca2+ channels but may more likely reflect modifications of the sarcomeres or sarcoplasmic reticulum.