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Effects of L‐type Ca 2+ Channel Facilitation on Ca 2+ Spark Activity in Fetal Ovine Pulmonary Arterial Myocytes
Author(s) -
Brunelle Alexander,
Romero Monica,
Puglisi Jose,
Bers Donald,
Izu Leighton,
Longo Lawrence,
Wilson Sean
Publication year - 2015
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.29.1_supplement.1031.10
Subject(s) - depolarization , ryanodine receptor , nifedipine , chemistry , myocyte , medicine , biophysics , membrane potential , extracellular , contraction (grammar) , calcium , endocrinology , biology , biochemistry
High extracellular K + concentrations are routinely used to depolarize arterial myocytes in order to drive ryanodine receptor (RyR) activity and enhance Ca 2+ spark activity. In the fetus, RyRs are important to vasodilation during birth. Previously, we showed that 30 mM K + increases RyR‐dependent Ca 2+ sparks by ~50% in fetal pulmonary arterial myocytes of sheep. Based on work of other laboratories, this increase in spark activity was presumed to be due to enhanced L‐type Ca 2+ channel (Ca L ) mediated Ca 2+ influx. FPL 64176 (FPL, 1 µM), a known Ca L agonist, causes a strong and sustained nifedipine sensitive contraction in fetal pulmonary arteries. Because of the potential linkage between membrane depolarization, Ca L activation, and Ca 2+ spark generation we examined whether Ca L facilitation with FPL would enhance spark activity in a similar manner to 30 mM K + . When we compared the percentage of cells with Ca 2+ sparks, we discovered that FPL‐facilitation of Ca L reduced spark activity, in comparison to our previously reported enhancement in sparks by 30 mM K + . These findings draw questions regarding the connection between membrane depolarization, Ca L facilitation, and resultant Ca 2+ spark activation. (Support from NIH and NSF)