Developmental Changes in Excitation–Contraction Mechanisms of the Mouse Ventricular Myocardium as Revealed by Functional and Confocal Imaging Analyses

Abstract

Abstract. Developmental changes in excitation-contraction mechanisms were examined in the ventricular myocardium from fetal, neonatal, and 1-, 2-, and 4-week-old mice. In isolated tissue, the negative inotropic effect of nifedipine decreased, while that of ryanodine increased with age. Action potential duration decreased with age, especially during the late fetal period. In ventricular cardiomyocytes, fluorescence imaging revealed that the sarcoplasmic reticulum increases progressively during pre-and postnatal development. t-Tubules were absent in the fetus and neonate, were observed only in the subsarcolemmal region at 1 week after birth, and were present throughout the cytoplasm at 2 and 4 weeks after birth. The amplitude of Ca 2+ transients, as well as its ryanodine-sensitive component, increased with age. In the neonate and 1-week-old mice, Ca 2+ at the cell center showed slower rise than the subsarcolemmal region, but in 2-and 4-week-old mice, Ca 2+ increased simultaneously across the entire width of the cell. These results suggest that in the mouse ventricular myocardium, the shortening of the action potential during the late fetal period and the development of t-tubule-sarcoplasmic reticulum coupling during the second postnatal week largely contribute to the developmental increase in the dependence of contraction on sarcoplasmic reticulum function.

Cholesterol depletion impairs contractile machinery in neonatal rat cardiomyocytes

“…Since extracellular Ca 2+ is critical for neonatal cardiomyocyte contraction4448495051, the interaction between the sarcolemma and extracellular milieu is crucial to guarantee homeostasis during contraction. We saw that cholesterol depletion increases membrane tension and disrupts caveolin-3 distribution.…”

“…For the neonatal cardiomyocyte case, extracellular Ca 2+ plays a fundamental role in contraction444849505164 since those cells lack T-tubules11. T-tubules are membranous cisternae networks that couple extracellular Ca 2+ entry to calcium-induced-calcium-release that is essential for adult ventricular cardiomyocytes contraction6566.…”

Cardiac T-Tubule Microanatomy and Function

“…In rodent and rabbit hearts, the process of t-tubule biogenesis initiates a few days after birth (82,83,187), along with the rise of the left ventricular pressure and working volume. Mature t-tubules are only fully developed by the end of the first month of life.…”

Effect of Terfenadine and Pentamidine on the hERG Channel and Its Intracellular Trafficking: Combined Analysis with Automated Voltage Clamp and Confocal Microscopy

“…[25][26][27][28] Coverslips with cells were placed in a chamber on the stage of the inverted microscope and perfused with HEPES-Tyrode solution of the following composition (mM): NaCl 143, KCl 5.4, MgCl 2 1.8, CaCl 2 2, NaH 2 PO 4 0.33, glucose 5.5 and HEPES 20. The solution was gassed with 100% O 2 .…”