Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles

Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 α-subunits underlies the fast transient Kv current (I_to,f) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of I_to,f in adult mouse ventricles, revealing an essential role for the Kv4.2 α-subunit in the generation of mouse ventricular I_to,f channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3−/−) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3−/− hearts. Voltage-clamp recordings revealed that functional I_to,f channels are expressed in Kv4.3−/− ventricular myocytes, and that mean I_to,f densities are similar to those recorded from wild-type cells. In addition, I_to,f properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3−/− and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3−/− ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular I_to,f channels.