Mechanism on Hsp70-induced stabilization of ion channel and its application to the treatment for atrial fibrillation

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We tested the effects of Hsp70 on the stability of Kv1.5 K^+ channel proteins using biochemical and electrophysiological techniques. Hsp70 and HSF-1 increased Kv1.5 proteins to be expressed in HeLa and COS7 cells, whereas either Hsp40, 27 or 90 did not. Hsp70 prolonged the half-life time of Kv1.5 without an increase of its ubiquitinated form, and increased the immunoreactivity of Kv1.5 in the endoplasmic reticulum and Golgi apparatus. Hsp70 also increased the amplitude of the ultrarapid delayed-rectifier K^+ current (Ik_ur) of transfected cells, which was abolished by pretreatment with brefeldin A or colchicine. Pretreatment with a Hsp70 inducer, geranyl-geranyl acetone (GGA), significantly increased Kv1.5 protein expression in COS7 cells. Pretreatment with GGA also significantly increased Ik_ur which is also abolished by brefeldin A or colchicine. In conclusion, Hsp70 stabilized the functional Kv1.5 protein.