Effect of the Membrane Environment on Pharmacologic Inhibition of hERG K

• Tác giả: Colleen E Clancy, Chase M Fiore, Robert D Harvey, Kate Quigley, Igor Vorobyov
• Ngôn ngữ: eng
• Ký hiệu phân loại: 363.737 Measures to prevent, protect against, limit effects of pollution
• Thông tin xuất bản: United States : JACC. Clinical electrophysiology , 2025
• Bộ sưu tập: NCBI
• ID: 62622

Tóm tắt

BACKGROUND: hERG encodes K OBJECTIVES: Because hERG channels reside in cholesterol rich lipid raft domains, we hypothesized that disrupting the membrane environment by depleting cholesterol might alter inhibition of channel activity by certain drugs. METHODS: We tested our hypothesis by examining the effect that depleting membrane cholesterol with methyl-β-cyclodextrin has on the ability of several compounds to inhibit hERG channels expressed in HEK293 cells. RESULTS: We found that cholesterol depletion significantly increased the sensitivity of the whole cell current to inhibition by ibutilide, while decreasing the currents sensitivity to dofetilide and amiodarone at negative membrane potentials. CONCLUSIONS: These results support the idea that the lipid environment of the plasma membrane plays a role in the ability of certain drugs to inhibit hERG channel activity. Differences in membrane cholesterol content may affect the ability of some hERG channel blockers to produce arrhythmogenic behavior.