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Ontogeny, ryanodine receptor‐mediated calcium sparks, and BK channel clustering in basilar arterial myocytes from long‐term hypoxic sheep (853.9)
Author(s) -
Glasgow Shane,
Tao Xiaoxiao,
Romero Monica,
Osman Noah,
Puglisi Jose,
Bers Donald,
Izu Leighton,
Longo Lawrence,
Hessinger David,
Wilson Sean
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.853.9
Subject(s) - bk channel , ryanodine receptor , medicine , endocrinology , myocyte , chemistry , basilar artery , calcium , biology
Ryanodine receptor (RyR) activity causes Ca 2+ sparks in cerebral arterial myocytes by activating adjacent Ca 2+ ‐activated K + (BK) channels, which can dilate arteries. Previous studies show ontogeny increases Ca 2+ sparks and long‐term hypoxia (LTH) increases BK channel activity. We hypothesized that BK channel activity is greater in arterial myocytes of the LTH fetus than adult due to greater spark activity, and because BK channel clustering is greater in regions where sparks occur. To address this hypothesis we examined spark activity and BK channel clustering to sites of potential spark activity. This was accomplished using line‐scan and immunofluorescence techniques, respectively, in basilar arteries from LTH fetal (FH) and adult sheep (AH) kept at 3,801 m for > 100 days. The percentage of myocytes with sparks was ~ 2‐fold greater in FH versus AH and unaffected by 30 mM K (30K). Spark amplitude was 7% greater in FH 30K versus AH 30K, while no spatial or temporal changes to sparks were observed. BK channels were 2‐3 times more clustered and ~1.5 times more co‐localized with cholera toxin B‐labeled clusters in FH. These data suggest greater BK targeting to potential sites of spark activity in FH myocytes. Elevated RyR‐dependent Ca 2+ spark activity in FH and altered patterns of BK distribution shed new light on the therapeutic potential of RyRs and BKs for treatment of cerebral vascular disease in newborns and adults. Grant Funding Source : Supported by NSF MRI 0923559, NIH HD‐069746, P01HD031226, R01HD003807, LLUSOM