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,I-f; and a non-inactivating, steady-state, K+ current, I-SS. 2. The properties of I-to,I-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,I-slow in ventricular cells, is detected in similar to 40 % of adult mouse atrial myocytes, and when ex-pressed, the density of this current component is substantially lower than the density of I-to,I-f or I-SS. 3. The similarity between atrial and ventricular I-to,I-f and the finding that both the Kv4 subfamily a subunits, Kv4.2 and Kv4.3, are expressed in wild-type mouse atria prompted us to determine if atrial I-to,I-f is affected in transgenic mice expressing a mutant Kv4.2 alpha subunit, Kv4.2W362F, that functions as a dominant negative. 4. Similar to findings in ventricular cells, electrophysiological recordings reveal that I-to,I-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,I-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,I-f is functionally eliminated. 7. The elimination of I-to,I-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.