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

Ruhr, Ilan M.; Shiels, Holly A.; Crossley, Dane A.; Galli, Gina L. J.

Abstract

Oxygen deprivation during embryonic development can permanently remodel the vertebrate heart, often causing cardiovascular abnormalities in adulthood. While this phenomenon is mostly damaging, recent evidence suggests developmental hypoxia produces stress-tolerant phenotypes in some ectothermic vertebrates. Embryonic common snapping turtles (Chelydra serpentina) subjected to chronic hypoxia display improved cardiac anoxia tolerance after hatching, which is associated with altered Ca2+ homeostasis in heart cells (cardiomyocytes). Here we examined the possibility that changes in Ca2+ cycling, through the sarcoplasmic reticulum (SR), underlie the developmentally programmed cardiac phenotype of snapping turtles. We investigated this hypothesis by isolating cardiomyocytes from juvenile turtles that developed in either normoxia (21% O2; “N21”) or chronic hypoxia (10% O2; “H10”) and subjected the cells to anoxia/reoxygenation, either in the presence or absence of SR Ca2+-cycling inhibitors. We simultaneously measured cellular shortening, intracellular [Ca2+], and intracellular pH (pHi). Under normoxic conditions, N21 and H10 cardiomyocytes shortened equally, but H10 Ca2+ transients (Δ[Ca2+]i) were twofold smaller than N21 cells, and SR inhibition only decreased N21 shortening and Δ[Ca2+]i. Anoxia subsequently depressed shortening, Δ[Ca2+]i, and pHi in control N21 and H10 cardiomyocytes, yet H10 shortening and Δ[Ca2+]i recovered to pre-anoxic levels, partly due to enhanced myofilament Ca2+ sensitivity. SR blockade abolished the recovery of anoxic H10 cardiomyocytes and potentiated decreases in shortening, Δ[Ca2+]i, and pHi. Our novel results provide the first evidence of developmental programming of SR function and demonstrate that developmental hypoxia confers a long-lasting, superior anoxia-tolerant cardiac phenotype in snapping turtles, by enhancing myofilament Ca2+ sensitivity and modifying SR function.

Citation

Ruhr, I. M., Shiels, H. A., Crossley, D. A., & Galli, G. L. J. (2024). Developmental programming of sarcoplasmic reticulum function improves cardiac anoxia tolerance in turtles. Journal of Experimental Biology, 227(20), Article jeb247434. https://doi.org/10.1242/jeb.247434

• Journal Article Type: Article
• Acceptance Date: Aug 27, 2024
• Online Publication Date: Sep 9, 2024
• Publication Date: Oct 15, 2024
• Deposit Date: Nov 14, 2024
• Publicly Available Date: Nov 14, 2024
• Journal: Journal of Experimental Biology
• Print ISSN: 0022-0949
• Publisher: Company of Biologists
• Peer Reviewed: Peer Reviewed
• Volume: 227
• Issue: 20
• Article Number: jeb247434
• DOI: https://doi.org/10.1242/jeb.247434