Abstract
Cs+‐sensitive K+ inward rectifier (Kir) ionic currents in macrophages are modulated during VCAM‐1/VLA‐4 interactions affecting macrophage function that may possibly contribute to atherogenesis (Colden‐Stanfield, 2009). While heavy metals, Cs+ and Ba2+, are known to nonspecifically block the Kir family of channels, specific blockade of the Kir2.1 subspecies by gambogic acid (GA) has only been recently demonstrated (Zaks‐Makhina et al., 2009). To determine the effect of GA on Kir currents in murine macrophages, we recorded patch‐clamp whole‐cell currents and resting membrane potential (RMP) in bone marrow‐derived macrophages (BMDMs) following a 3‐h pretreatment with GA or its vehicle, DMSO. In the absence of exogenous GA 97% of BMDMs (32 of 33 cells) possessed Kir currents that were elicited during hyperpolarization and an RMP of −57 mV. When the cells were incubated with GA (500 nM) for 3 h, Kir currents were completely inhibited (19 of 19 cells). RMP of cells was significantly depolarized to −11 mV compared to control cells. Exposure to DMSO (0.0005%) for 3 h did not alter Kir currents. As a comparison, exogenous Cs+ (10 mM for 30 min) completely blocked Kir currents but only depolarized the membrane to −46 mV. This data and the lack of necrotic or programmed cell death in the presence of GA indicate that Kir2.1 channels underlie Kir whole‐cell currents in BMDMs. This research was supported by NHLBI K01 HL076628.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call