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Elimination of the transient outward current and action potential prolongation in mouse atrial myocytes expressing a dominant negative Kv4 α subunit
Author(s) -
Xu Haodong,
Li Huilin,
Nerbonne Jeanne M.
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0011o.x
Subject(s) - cardiac transient outward potassium current , myocyte , medicine , electrophysiology , patch clamp , depolarization , voltage clamp , endocrinology , atrial myocytes , chemistry , genetically modified mouse , knockout mouse , potassium channel , biology , biophysics , transgene , receptor , biochemistry , gene
1 Analyses of whole‐cell voltage‐clamp recordings from isolated adult (C57BL6) mouse atrial myocytes reveal the presence of two prominent Ca 2+ ‐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.