Long-term hypoxia modulates depolarization activation of BK Ca currents in fetal sheep middle cerebral arterial myocytes.

Autor:	Nelapudi N; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Boskind M; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Hu XQ; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Mallari D; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Chan M; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Wilson D; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Romero M; Advanced Imaging and Microscopy Core, Loma Linda University School of Medicine, Loma Linda, CA, United States., Albert-Minckler E; Advanced Imaging and Microscopy Core, Loma Linda University School of Medicine, Loma Linda, CA, United States., Zhang L; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Blood AB; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Wilson CG; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States., Puglisi JL; Department of Biostatistics, California Northstate University School of Medicine, Elk Grove, CA, United States., Wilson SM; Lawrence D Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, United States.; Advanced Imaging and Microscopy Core, Loma Linda University School of Medicine, Loma Linda, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2024 Nov 05; Vol. 15, pp. 1479882. Date of Electronic Publication: 2024 Nov 05 (Print Publication: 2024).
DOI:	10.3389/fphys.2024.1479882
Abstrakt:	Introduction: Previous evidence indicates that gestational hypoxia disrupts cerebrovascular development, increasing the risk of intracranial hemorrhage and stroke in the newborn. Due to the role of cytosolic Ca 2+ in regulating vascular smooth muscle (VSM) tone and fetal cerebrovascular blood flow, understanding Ca 2+ signals can offer insight into the pathophysiological disruptions taking place in hypoxia-related perinatal cerebrovascular disease. This study aimed to determine the extent to which gestational hypoxia disrupts local Ca 2+ sparks and whole-cell Ca 2+ signals and coupling with BK Ca channel activity. Methods: Confocal imaging of cytosolic Ca 2+ and recording BK Ca currents of fetal sheep middle cerebral arterial (MCA) myocytes was performed. MCAs were isolated from term fetal sheep (∼140 days of gestation) from ewes held at low- (700 m) and high-altitude (3,801 m) hypoxia (LTH) for 100+ days of gestation. Arteries were depolarized with 30 mM KCl (30K), in the presence or absence of 10 μM ryanodine (Ry), to block RyR mediated Ca 2+ release. Results: Membrane depolarization increased Ry-sensitive Ca 2+ spark frequency in normoxic and LTH groups along with BK Ca activity. LTH reduced Ca 2+ spark and whole-cell Ca 2+ activity and induced a large leftward shift in the voltage-dependence of BK Ca current activation. The influence of LTH on the spatial and temporal aspects of Ca 2+ sparks and whole-cell Ca 2+ responses varied. Discussion: Overall, LTH attenuates Ca 2+ signaling while increasing the coupling of Ca 2+ sparks to BK Ca activity; a process that potentially helps maintain oxygen delivery to the developing brain. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Nelapudi, Boskind, Hu, Mallari, Chan, Wilson, Romero, Albert-Minckler, Zhang, Blood, Wilson, Puglisi and Wilson.)
Databáze:	MEDLINE
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