Long Term Hypoxia Negatively Influences Ca2+ Signaling in Basilar Arterial Myocytes of Fetal and Adult Sheep

Abstract

Gestational long term hypoxia (LTH) is a common prenatal stress caused by maternal anemia, high altitude living, smoking, and other disorders. Such gestational LTH can lead to a variety of cerebrovascular disorders in the neonate that compromise brain blood flow. Local and whole‐cell Ca2+ signals are important to the regulation of cerebrovascular tone. Rapid and localized Ca2+ transients, often referred to as sparks, activate large‐conductance K+ channels (BK), which dilate vessels. Whole‐cell Ca2+ oscillations, in comparison, are important to arterial contraction. Previous work shows that LTH and post‐natal maturity influence BK channel function in basilar arteries, arterial wall Ca2+ signals, cerebrovascular tone, as well as brain blood flow. We hypothesize that LTH‐dependent changes in spontaneous and depolarization mediated Ca2+ sparks and whole‐cell oscillations are important to BK channel activity, arterial wall Ca2+ signals, and vascular reactivity changes our group has previously observed. To begin evaluating the role of individual myocyte Ca2+ signals to the observed changes in cerebrovascular function, we isolated basilar arteries from adult and near term fetal (~141 gestational days) normoxic and hypoxic sheep that were raised at 3,800 m. for 110+ days. Cytosolic Ca2+ signals were examined in individual myocytes of intact arterial preparations loaded with fluo‐4 using laser scanning confocal microscopy techniques. Ca2+ spark activity as well as whole‐cell oscillations were enhanced by depolarizing myocytes with 30 mM K+. Maturation increased Ca2+ spark activity and depolarization‐dependent oscillations. LTH decreased oscillatory activity in fetal and adult animals but only spark frequency in adult myocytes. LTH decreased the area under the curve for Ca2+ oscillations independent of age as well as suppressed the ability of adult myocytes to respond to membrane depolarization. Depolarization, maturation, and LTH also influenced the spatial and temporal relationships of the Ca2+ oscillations. Overall, these observations illustrate that maturation and gestation at high‐altitude modify local and whole‐cell Ca2+ signaling, which likely contribute to adjustments in BK channel function, arterial wall Ca2+ signals, vasoreactivity, and cerebral blood flow that our group has examined in the past.Support or Funding InformationThis material is based upon work supported by NIH grants P01HD083132 (LZ). Imaging was performed in the LLUSM Advanced Imaging and Microscopy Core with support of NSF Grant MRI‐DBI 0923559 and the Loma Linda University School of Medicine.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.