Gestational long-term hypoxia alters L-type Ca²⁺channel-mediated Ca²⁺spark activity in newborn cerebral arteries

Gestational long-term hypoxia (LTH) impacts cerebrovascular development, increasing the risk of intracranial hemorrhage and stroke in newborns. This study investigated the influence of LTH on L-type Ca 2+ channel regulation of ryanodine receptor-mediated Ca 2+ sparks in basilar arterial myocytes of newborn sheep. Control animals were maintained at low altitude (~350m), while hypoxic animals were exposed to 3801m for 110+ days. Basilar arteries were isolated from 5-7-day-old sheep that were kept in normoxic or hypoxic environments mimicking the high altitude environment after birth. Cytosolic Ca 2+ activity was measured using Fluo-4 linescan confocal microscopy. Myocytes were depolarized with 30 mM KCl (30K), with or without 1 μM nifedipine (NIF) to inhibit L-type Ca 2+ channel activity. Results showed that LTH dysregulated Ca 2+ spark activity in basilar arterial myocytes, decreasing activity in the 30K group, similar to previous observations in fetal vessels, a process which may impair vasodilatory responses. Notably, NIF treatment augmented Ca 2+ spark activity in myocytes from normoxic but not hypoxic newborn vessels, suggesting a complex role of L-type Ca 2+ channels in regulating Ca 2+ spark activity during the newborn period. Additionally, complex changes in spatial-temporal Ca 2+ spark responses were observed following LTH. Further research is needed to elucidate the role of L-type Ca 2+ channels in Ca 2+ spark activity in newborn cerebral vessels and to understand the epigenetic processes involved in LTH-induced disruption of Ca 2+ activity and its impact on vasoreactivity. This study also highlights the importance of exploring alternative pathways that may trigger Ca 2+ sparks and determining the biological significance of changes in Ca 2+ spark activity in relation to LTH and cerebrovascular function in neonates. Support from the NSF, NIH, LLU School of Medicine, Advanced Imaging and Microscopy Facility, and SURF programs through LLU (EP) and University of Redlands (JC) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.