Developmental programming of sarcoplasmic reticulum function improves cardiac anoxia tolerance in turtles.

Area of Science:

• Cardiovascular Physiology
• Developmental Biology
• Comparative Physiology

Background:

• Embryonic oxygen deprivation can cause lasting heart defects.
• However, developmental hypoxia can create stress-tolerant phenotypes in some ectotherms.
• Snapping turtles exposed to hypoxia during development show enhanced cardiac anoxia tolerance post-hatching.

Purpose of the Study:

• To investigate if altered calcium (Ca2+) cycling via the sarcoplasmic reticulum (SR) underlies the developmentally programmed cardiac phenotype in snapping turtles.
• To determine the role of SR function in the enhanced anoxia tolerance observed in turtles developed under hypoxic conditions.

Main Methods:

• Isolated cardiomyocytes from juvenile snapping turtles (Chelydra serpentina) developed in normoxia (21% O2) or chronic hypoxia (10% O2).
• Cells were subjected to anoxia/reoxygenation with and without SR Ca2+-cycling inhibitors.
• Simultaneous measurements of cellular shortening, intracellular Ca2+ concentration ([Ca2+]i), and intracellular pH (pHi).

Main Results:

• Hypoxic-developed (H10) cardiomyocytes exhibited smaller Ca2+ transients and blunted SR inhibition effects under normoxia compared to normoxic-developed (N21) cells.
• Anoxia depressed cardiac function in both groups, but H10 cells showed recovery of shortening and [Ca2+]i, partly due to increased myofilament Ca2+ sensitivity.
• SR blockade abolished the recovery in H10 cells, indicating a critical role for SR function in conferring anoxia tolerance.

Conclusions:

• Developmental hypoxia permanently programs sarcoplasmic reticulum (SR) function in snapping turtle hearts.
• This programming enhances cardiac anoxia tolerance through modified SR function and increased myofilament Ca2+ sensitivity.
• The study provides the first evidence of SR programming contributing to a superior, long-lasting anoxia-tolerant cardiac phenotype.