Potassium Channel Activity in Human Coronary Artery Smooth Muscle Cells is Regulated by Cyclic Nucleotide-dependent Phosphorylation
Location
Georgia Campus
Start Date
7-5-2014 1:00 PM
Description
Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. For example, although both estrogens and androgens are vasodilators, there is evidence that these hormones may either prevent or contribute to CVD. We have demonstrated that gondal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKCa) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved in this process remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) / dephosphorylation (via phosphoprotein phosphatase 2A) regulates BKCa channel activity in human coronary artery smooth muscle cells (HCASMC). BKCa channel activity was recorded from single HCASMC (Lonza/Clonetics) via cell-attached and inside-out membrane patches using the patch-clamp technique. We found channel activity was stimulated by increasing either cAMP or cGMP in HCASMC, but that the stimulatory effect was mediated predominately via the cGMP-dependent protein kinase. These findings demonstrate that gonadal steroids and other hormones can regulate arterial function via cyclic nucleotide-dependent phosphorylation of BKCa channels, and may thereby influence cardiovascular function. We propose that modulation of BKCa channels via hormone- or drug-induced phosphorylation could be a novel therapeutic means of helping to lower the risk of CVD in both males and females.
Potassium Channel Activity in Human Coronary Artery Smooth Muscle Cells is Regulated by Cyclic Nucleotide-dependent Phosphorylation
Georgia Campus
Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. For example, although both estrogens and androgens are vasodilators, there is evidence that these hormones may either prevent or contribute to CVD. We have demonstrated that gondal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKCa) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved in this process remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) / dephosphorylation (via phosphoprotein phosphatase 2A) regulates BKCa channel activity in human coronary artery smooth muscle cells (HCASMC). BKCa channel activity was recorded from single HCASMC (Lonza/Clonetics) via cell-attached and inside-out membrane patches using the patch-clamp technique. We found channel activity was stimulated by increasing either cAMP or cGMP in HCASMC, but that the stimulatory effect was mediated predominately via the cGMP-dependent protein kinase. These findings demonstrate that gonadal steroids and other hormones can regulate arterial function via cyclic nucleotide-dependent phosphorylation of BKCa channels, and may thereby influence cardiovascular function. We propose that modulation of BKCa channels via hormone- or drug-induced phosphorylation could be a novel therapeutic means of helping to lower the risk of CVD in both males and females.