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Cardiac sarcoplasmic reticular function in rats with chronic heart failure following myocardial infarction
F Yamaguchi1, A Sanbe, S Takeo
1Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Insights
Chronic heart failure (CHF) in rats impairs sarcoplasmic reticulum (SR) function, reducing calcium uptake and release. This dysfunction, linked to SR Ca2+-release channel down-regulation, contributes to cardiac issues post-myocardial infarction.
Area of Science:
- Cardiology
- Cellular Physiology
- Molecular Biology
Background:
- Chronic heart failure (CHF) significantly impacts cardiac function.
- Sarcoplasmic reticulum (SR) plays a critical role in regulating intracellular calcium levels essential for heart muscle contraction.
- Dysfunction in SR calcium handling is implicated in the pathophysiology of heart failure.
Purpose of the Study:
- To investigate the functional alterations of the sarcoplasmic reticulum (SR) in a rat model of chronic heart failure (CHF).
- To examine the effects of myocardial infarction on SR calcium uptake, release, and Ca2+-release channel activity.
Main Methods:
- Induction of CHF in rats via coronary artery ligation, confirmed by left ventricular infarction and increased end-diastolic pressure.
- Assessment of skinned cardiac fiber contractility under varying calcium (Ca2+) concentrations and caffeine stimulation.
- Measurement of [3H]Ryanodine binding activity in cardiac homogenates and SR-enriched fractions.
Main Results:
- Skinned fibers from CHF rats showed reduced developed force when preloaded with Ca2+ or exposed to caffeine, indicating impaired SR function.
- A significant decrease in Ca2+ uptake rate and Ca2+ release ability of the SR was observed in failing hearts.
- [3H]Ryanodine binding, reflecting Ca2+-release channel activity, was significantly reduced in both homogenates and SR fractions of CHF rats.
Conclusions:
- The study demonstrates impaired SR Ca2+ uptake and release in a rat model of CHF.
- Down-regulation of the SR Ca2+-release channel contributes to reduced Ca2+ release from the SR.
- These SR functional deficits play a significant role in cardiac dysfunction following myocardial infarction.
Abstract:
Sarcoplasmic reticular function of rats with chronic heart failure (CHF) following coronary artery ligation was examined. The coronary artery ligation produced 43% infarction of the left ventricle and increased left ventricular end-diastolic pressure 8 weeks after the operation, suggesting the development of CHF by this period. The developed force transients of the skinned fiber of coronary artery-ligated rats were decreased when the skinned fiber was preloaded for 0.25-0.5 min with 10(-5)M Ca2+ (53-70%) and when preloaded with 10(-6)M Ca2+ and then exposed to 0.1-1 mM caffeine (39-87%). The results suggest that the rate of Ca2+ uptake by the sarcoplasmic reticulum (SR) and its ability to release Ca2+ were reduced in the failing heart. [3H]Ryanodine binding activities in homogenates and SR-enriched fractions were significantly reduced in the coronary artery-ligated group (32% and 21%, respectively). The results suggest that the amount of Ca2+ released from SR decreased due to decreased Ca2+ uptake rate of SR and down-regulation of the SR Ca(2+)-release channel, which contributes to cardiac dysfunction in failing hearts following acute myocardial infarction.