Elimination of the transient outward current and action potential prolongation in mouse atrial myocytes expressing a dominant negative Kv4 α subunit

1. Analyses of whole-cell voltage-clamp recordings from isolated adult (C57BL6) mouse atrial myocytes reveal the presence of two prominent Ca²⁺-independent depolarization-activated K⁺ currents: a rapidly activating and inactivating, transient outward K⁺ current, I(to,f); and a non-inactivating, steady-state, K⁺ current, I(SS). 2. The properties of I(to,f) and I(SS) in adult mouse atrial myocytes are similar to those of the analogous currents recently described in detail in adult mouse ventricular cells. A slowly inactivating K⁺ current, which is similar to I(K,slow) in ventricular cells, is detected in ~40% of adult mouse atrial myocytes, and when expressed, the density of this current component is substantially lower than the density of I(to,f) or I(SS). 3. The similarity between atrial and ventricular I(to,f) and the finding that both the Kv4 subfamily α subunits, Kv4.2 and Kv4.3, are expressed in wild-type mouse atria prompted us to determine if atrial I(to,f) is affected in transgenic mice expressing a mutant Kv4.2 α subunit, Kv4.2W362F, that functions as a dominant negative. 4. Similar to findings in ventricular cells, electrophysiological recordings reveal that I(to,f) is selectively eliminated in atrial myocytes isolated from transgenic mice expressing Kv4.2W362F, thereby demonstrating directly that Kv4 subfamily members also underlie mouse atrial I(to,f). 5. Neither the steady-state, non-inactivating K⁺ current I(SS), nor the inwardly rectifying K⁺ current I(K1), in atrial myocytes is affected by the expression of Kv4.2W362F. 6. In contrast to previous findings in Kv4.2W362F-expressing mouse ventricular myocytes, there is no evidence that electrical remodelling occurs in atrial cells when I(to,f) is functionally eliminated. 7. The elimination of I(to,f) is accompanied by marked increases in atrial action potential durations, although no electrocardiographic abnormalities attributable to, or suggestive of, altered atrial functioning are evident in Kv4.2W362F-expressing animals.