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Molecular basis of transient outward K + current diversity in mouse ventricular myocytes
Author(s) -
Guo Weig,
Xu Haodong,
London Barry,
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.1469-7793.1999.00587.x
Subject(s) - cardiac transient outward potassium current , myocyte , apex (geometry) , medicine , genetically modified mouse , biology , electrophysiology , chemistry , microbiology and biotechnology , endocrinology , transgene , anatomy , patch clamp , gene , biochemistry
1 Two kinetically and pharmacologically distinct transient outward K + currents, referred to as I to,f and I to,s , have been distinguished in mouse left ventricular myocytes. I to,f is present in all left ventricular apex cells and in most left ventricular septum cells, whereas I to,s is identified exclusively in left ventricular septum cells. 2 Electrophysiological recordings from ventricular myocytes isolated from animals with a targeted deletion of the Kv1.4 gene (Kv1.4 −/− mice) reveal that I to,s is undetectable in cells isolated from the left ventricular septum ( n = 26 ). I to,f density in both apex and septum cells, in contrast, is not affected by deletion of Kv1.4.3 Neither the 4‐AP‐sensitive, slowly inactivating K + current, I K,slow , nor the steady‐state non‐inactivating K + current, I SS , is affected in Kv1.4 −/− mouse left ventricular cells. 4 In myocytes isolated from transgenic mice expressing a dominant negative Kv4.2 α subunit, Kv4.2W362F, I to,f is eliminated in both left ventricular apex and septum cells. In addition, a slowly inactivating transient outward K + current similar to I to,s in wild‐type septum cells is evident in myocytes isolated from left ventricular apex of Kv4.2W362F‐expressing transgenics. The density of I to,s in septum cells, however, is unaffected by Kv4.2W362F expression. 5 Western blots of fractionated mouse ventricular membrane proteins reveal a significant increase in Kv1.4 protein level in Kv4.2W362F‐expressing transgenic mice. The protein levels of other Kv α subunits, Kv1.2 and Kv2.1, in contrast, are not affected by the expression of the Kv4.2W362F transgene. 6 The results presented here demonstrate that the molecular correlates of I to,f and I to,s in adult mouse ventricle are distinct. Kv1.4 underlies mouse ventricular septum I to,s , whereas Kv α subunits of the Kv4 subfamily underlie mouse ventricular apex and septum I to,f . The appearance of the slow transient outward K + current in Kv4.2W362F‐expressing left ventricular apex cells with properties indistinguishable from I to,s in wild‐type cells is accompanied by an increase in Kv1.4 protein expression, suggesting that the upregulation of Kv1.4 underlies the observed electrical remodeling in Kv4.2W362F‐expressing transgenics.