Published online before print January 20, 2005, doi: 10.1161/01.RES.0000156890.25876.63
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Submitted on July 22, 2004
Revised on January 7, 2005
Accepted on January 12, 2005
Accessory Kv
1 Subunit Differentially Modulates the Functional Expression of Voltage-Gated K+ Channels in Mouse Ventricular Myocytes
Franck Aimond ;
From the Department of Molecular Biology and Pharmacology (F.A., J.M.N.), Washington University School of Medicine, St Louis, Mo; and Wyeth-Ayerst Research (S.P.K., K.J.R.), Princeton, NJ.
* To whom correspondence should be addressed. E-mail: jnerbonne{at}msnotes.wustl.edu.
Voltage-gated K+ (Kv) channel accessory (
) subunits associate with pore-forming Kv 
subunits and modify the properties and/or cell surface expression of Kv channels in heterologous expression systems. There is very little presently known, however, about the functional role(s) of Kv subunits in the generation of native cardiac Kv channels. Exploiting mice with a targeted disruption of the Kv1 gene (Kv1-/-), the studies here were undertaken to explore directly the role of Kv1 in the generation of ventricular Kv currents. Action potential waveforms and peak Kv current densities are indistinguishable in myocytes isolated from the left ventricular apex (LVA) of Kv1-/- and wild-type (WT) animals. Analysis of Kv current waveforms, however, revealed that mean±SEM Ito,f density is significantly (P
0.01) lower in Kv1-/- (21.0±0.9 pA/pF; n=68), than in WT (25.3±1.4 pA/pF; n=42), LVA myocytes, and that mean±SEM IK,slow density is significantly (P0.01) higher in Kv1-/- (19.1±0.9 pA/pF; n=68), compared with WT (15.9±0.7 pA/pF; n=42), LVA cells. Pharmacological studies demonstrated that the TEA-sensitive component of IK,slow, IK,slow2, is selectively increased in Kv1-/- LVA myocytes. In parallel with the alterations in Ito,f and IK,slow2 densities, Kv4.3 expression is decreased and Kv2.1 expression is increased in Kv1-/- ventricles. Taken together, these results demonstrate that Kv1 differentially regulates the functional cell surface expression of myocardial Ito,f and IK,slow2 channels.
Key words: potassium channels • Kv accessory subunits • Kv
•
Ito,f •
IK,slow
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