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

Autor:	Ruhr IM; Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester M13 9NT, UK.; School of Science, Engineering, & Environment, University of Salford, Salford M5 4NT, UK., Shiels HA; Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester M13 9NT, UK., Crossley DA 2nd; Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA., Galli GLJ; Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester M13 9NT, UK.
Jazyk:	angličtina
Zdroj:	The Journal of experimental biology [J Exp Biol] 2024 Oct 15; Vol. 227 (20). Date of Electronic Publication: 2024 Oct 30.
DOI:	10.1242/jeb.247434
Abstrakt:	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, in either the presence or absence of SR Ca2+-cycling inhibitors. We simultaneously measured cellular shortening, intracellular Ca2+ concentration ([Ca2+]i), and intracellular pH (pHi). Under normoxic conditions, N21 and H10 cardiomyocytes shortened equally, but H10 Ca2+ transients (Δ[Ca2+]i) were twofold smaller than those of 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 modifying SR function and enhancing myofilament Ca2+ sensitivity. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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