| Autor: |
Nikitha Nelapudi, Madison Boskind, Xiang-Qun Hu, David Mallari, Michelle Chan, Devin Wilson, Monica Romero, Eris Albert-Minckler, Lubo Zhang, Arlin B. Blood, Christopher G. Wilson, Jose Luis Puglisi, Sean M. Wilson |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Frontiers in Physiology, Vol 15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1664-042X |
| DOI: |
10.3389/fphys.2024.1479882 |
| Popis: |
IntroductionPrevious 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 Ca2+ in regulating vascular smooth muscle (VSM) tone and fetal cerebrovascular blood flow, understanding Ca2+ 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 Ca2+ sparks and whole-cell Ca2+ signals and coupling with BKCa channel activity.MethodsConfocal imaging of cytosolic Ca2+ and recording BKCa 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 Ca2+ release.ResultsMembrane depolarization increased Ry-sensitive Ca2+ spark frequency in normoxic and LTH groups along with BKCa activity. LTH reduced Ca2+ spark and whole-cell Ca2+ activity and induced a large leftward shift in the voltage-dependence of BKCa current activation. The influence of LTH on the spatial and temporal aspects of Ca2+ sparks and whole-cell Ca2+ responses varied.DiscussionOverall, LTH attenuates Ca2+ signaling while increasing the coupling of Ca2+ sparks to BKCa activity; a process that potentially helps maintain oxygen delivery to the developing brain. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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