Klotho sensitivity of the hERG channel

• Coexpression of klotho enhances activity of cardiac K+-channel hERG.
• Coexpression of klotho increases hERG protein abundance in the cell membrane.
• The effect of expressed klotho is mimicked by recombinant klotho protein.
• The effect of klotho is blunted by d-saccharic acid-1,4-lactone.

Klotho, a hormone and enzyme, is a powerful regulator of ageing and life span. Klotho deficiency leads to cardiac arrythmia and sudden cardiac death. We thus explored whether klotho modifies cardiac K+-channel hERG. Current was determined utilizing dual electrode voltage clamp and hERG protein abundance utilizing immunohistochemistry and chemiluminescence in Xenopus oocytes expressing hERG with or without klotho. Coexpression of klotho increased cell membrane hERG-protein abundance and hERG current at any given voltage without significantly modifying the voltage required to activate the channel. The effect of klotho coexpression was mimicked by recombinant klotho protein and reversed by β-glucuronidase-inhibitor d-saccharic acid-1,4-lactone.