TY - JOUR
T1 - Influence of Maturation on Ca2+ Waveform Modulation by c-AMP and c-GMP in Pulmonary Arterial Smooth Muscle of Sheep
AU - Paez, Ricardo
AU - Romero, Monica
AU - Dobyns, Abby
AU - Francis, Michael
AU - Taylor, Mark
AU - Longo, Lawrence
AU - Wilson, Christopher
AU - Wilson, Sean
PY - 2015/4/1
Y1 - 2015/4/1
N2 - One critical feature of the pulmonary vasculature is the ability to vasodilate in response to PKA and PKG signaling, which are important at birth and later in life. These kinases are activated by cAMP and cGMP respectfully, which can modulate Ca 2+ release through enhanced activity of ryanodine receptors (RyRs) and Sarco/Endoplasmic Reticulum Ca 2+ ‐ATPase (SERCA) pumps. To test the relevance of maturity on unstimulated Ca 2+ waveforms and determine the effects of c‐AMP and c‐GMP on their function, we examined the influence of 3‐isobutyl‐1‐methyl xanthine (IBMX), a PDE inhibitor that primarily increases c‐AMP, as well as 8‐Br‐c‐AMP and 8‐Br‐c‐GMP that are degradation resistant c‐AMP and c‐GMP isoforms. Cytosolic Ca 2+ wave activity was measured in fetal and adult sheep via confocal Ca 2+ imaging of individual myocytes in artery strips. Maturation increased the percentage of responsive cells independent of altitude while IBMX, 8‐Br‐c‐AMP, and 8‐Br‐c‐GMP each failed to alter the number of active myocytes in both groups. c‐GMP increased net Ca 2+ wave activity through temporal changes while IBMX and c‐AMP had minimal effect on Ca 2+ activity. Yet, c‐AMP increased the interaction between regions of interest (ROIs) in adults but not fetuses. The firing of ROIs near to one another was enhanced by cAMP in adults but reduced in fetuses, while c‐GMP increased this in both. Even though future research is required to fully comprehend the role of Ca 2+ signals during normal cellular maturation, our results suggest that c‐GMP amplifies these Ca 2+ signals.
AB - One critical feature of the pulmonary vasculature is the ability to vasodilate in response to PKA and PKG signaling, which are important at birth and later in life. These kinases are activated by cAMP and cGMP respectfully, which can modulate Ca 2+ release through enhanced activity of ryanodine receptors (RyRs) and Sarco/Endoplasmic Reticulum Ca 2+ ‐ATPase (SERCA) pumps. To test the relevance of maturity on unstimulated Ca 2+ waveforms and determine the effects of c‐AMP and c‐GMP on their function, we examined the influence of 3‐isobutyl‐1‐methyl xanthine (IBMX), a PDE inhibitor that primarily increases c‐AMP, as well as 8‐Br‐c‐AMP and 8‐Br‐c‐GMP that are degradation resistant c‐AMP and c‐GMP isoforms. Cytosolic Ca 2+ wave activity was measured in fetal and adult sheep via confocal Ca 2+ imaging of individual myocytes in artery strips. Maturation increased the percentage of responsive cells independent of altitude while IBMX, 8‐Br‐c‐AMP, and 8‐Br‐c‐GMP each failed to alter the number of active myocytes in both groups. c‐GMP increased net Ca 2+ wave activity through temporal changes while IBMX and c‐AMP had minimal effect on Ca 2+ activity. Yet, c‐AMP increased the interaction between regions of interest (ROIs) in adults but not fetuses. The firing of ROIs near to one another was enhanced by cAMP in adults but reduced in fetuses, while c‐GMP increased this in both. Even though future research is required to fully comprehend the role of Ca 2+ signals during normal cellular maturation, our results suggest that c‐GMP amplifies these Ca 2+ signals.
UR - http://www.fasebj.org/doi/abs/10.1096/fasebj.29.1_supplement.1031.11
UR - https://www.mendeley.com/catalogue/a0f36e74-6aa0-3f6d-b4c1-95d7141d9b9a/
U2 - 10.1096/fasebj.29.1_supplement.1031.11
DO - 10.1096/fasebj.29.1_supplement.1031.11
M3 - Meeting abstract
VL - 29
SP - 1031.11
JO - The FASEB Journal
JF - The FASEB Journal
IS - S1
ER -