期刊
CELL BIOCHEMISTRY AND BIOPHYSICS
卷 39, 期 3, 页码 183-193出版社
HUMANA PRESS INC
DOI: 10.1385/CBB:39:3:183
关键词
human ether-a-go-go-related gene; K+ ion channel; heart; I-Kr; delayed rectifier; pH; ischemia; gating; activation; deactivation
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL062465, R01HL019216, R37HL019216] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL-19216, 8 R01 HL-62465-05] Funding Source: Medline
HERG (Human ether-a-go-go-related gene) potassium channels are crucial for cardiac action potential repolarization. HERG channels are also found in neuronal and tumor cells The effect of pH(o) on HERG is of clinical significance because of changes in pH during myocardial ischemia, inflammation, and respiratory alkalosis. We present evidence for the presence of multiple proton binding sites in HERG. Extracellular protons bind rapidly and reversibly to affect both activation and deactivation. However, these effects occur in two distinct pH(o) ranges. The deactivation rate has a pK(a) of 6.76 +/- 0.02 compared to pK(a) of 5.50 +/- 0.02 for changes in current suppression, which suggests the presence of at least two proton binding sites on HERG with functionally distinct properties.
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