AI Article Synopsis
- The hKv1.5 potassium channel is crucial for cardiac action potential repolarization, but its activity is diminished in chronic atrial fibrillation patients.
- Long-term treatment with 4-Aminopyridine (4-AP) in HEK cells enhanced hKv1.5 protein levels, improved its glycosylation, and increased the associated potassium current.
- The research identified the Ile508 residue in the hKv1.5 channel as significant for 4-AP's inhibitory effect, suggesting potential for developing treatments to restore potassium current in atrial fibrillation patients.
Article Abstract
The human Kv1.5 channel (hKv1.5) produces the ultrarapid delayed rectifier potassium current (I), which is important for determining the repolarization of action potential in the cardiac atrium. However, the expression of I is reduced in patients with chronic atrial fibrillation. 4-Aminopyridine (4-AP) can specifically suppress I, suggesting that it modifies hKv1.5 as a chaperone molecule. Herein, the effects of long-term 4-AP treatment on hKv1.5 protein expression and function were investigated in HEK cells. 4-AP treatment (24 h) improved hKv1.5 protein levels, promoted hKv1.5 glycosylation, and facilitated the hKv1.5 current in a time-dependent manner. Long-term 4-AP treatment also markedly enhanced hKv1.5 localization in the cell membrane, endoplasmic reticulum, and Golgi. Importantly, the Ile508 residue located in the hKv1.5 channel pore was found to be important for 4-AP inhibitory activity. These results provide insight into developing hKv1.5 channel blocker that can functionally rescue I in patients with chronic atrial fibrillation.
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| http://dx.doi.org/10.1016/j.ejphar.2018.12.022 | DOI Listing |
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