- 作者: I-Shan Chen; Zen-Kong Dai; Donald G Welsh; Ing-Jun Chen; Bin-Nan Wu
- 作者服務機構: Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: This study investigates whether protein kinase G (PKG), protein kinase A (PKA) and
protein kinase C (PKC) are involved in the regulatory mechanisms of store-operated channel (SOC) in
pulmonary arteries.
Methods: Pulmonary artery smooth muscle cells (PASMCs) were enzymatically dissociated from rat
intralobar pulmonary arteries. Whole cell, cell-attached and inside-out patch-clamp electrophysiology
were used to monitor SOCs in isolated PASMCs.
Results: Initially the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA, 10 μM) initiated a whole cell
current that was reduced by the SOC blocker SKF-96365 (10 μM). Subsequent work using both
cell-attached and whole cell configurations revealed that the PKG and PKA inhibitors, KT5823 (3 μM)
and H-89 (10 μM), also stimulated SOC activity; this augmentation was attenuated by the SOC blockers
SKF-96365 (10 μM) and Ni2+ (0.1 mM). Finally using the inside-out configuration, the PKC activator
phorbol 12-myristate 13-acetate (PMA, 10 μM) was confirmed to modestly stimulate SOC activity
although this augmentation appeared to be more substantial following the application of 10 μM inositol
1,4,5-triphosphate (Ins(1,4,5)P3).
Conclusions: SOC activity in PASMCs was stimulated by the inhibition of PKG and PKA and the
activation of PKC. Our findings suggest that the SOC could be a substrate of these protein kinases,
which therefore would regulate the intracellular concentration of calcium and pulmonary arteriopathy
via SOC. - 中文關鍵字: --
- 英文關鍵字: --