Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A

Abstract

Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P<0.05 vs. CON, n=10). Ba2+(50 μM) decreased Kir2.x currents (−2.13±0.23 pA/pF, P<0.05 vs. CON, n=10), which were promoted by PDGF-BB (−6.98±1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor β (PDGF-BBRβ) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs.