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(Circulation Research. 2005;96:451.)
© 2005 American Heart Association, Inc.

Cellular Biology

Accessory Kvß₁ Subunits Differentially Modulate the Functional Expression of Voltage-Gated K⁺ Channels in Mouse Ventricular Myocytes

Franck Aimond, Seung P. Kwak, Kenneth J. Rhodes, Jeanne M. Nerbonne

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.

Correspondence to Jeanne M. Nerbonne, Department of Molecular Biology and Pharmacology, Washington University Medical School, 660 South Euclid Ave, Box 8103, St Louis, MO 63110-1093. E-mail jnerbonne{at}msnotes.wustl.edu

Voltage-gated K⁺ (Kv) channel accessory (ß) 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 ß subunits in the generation of native cardiac Kv channels. Exploiting mice with a targeted disruption of the Kvß₁ gene (Kvß₁^–/–), the studies here were undertaken to explore directly the role of Kvß₁ 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 Kvß₁^–/– and wild-type (WT) animals. Analysis of Kv current waveforms, however, revealed that mean±SEM I_to,f density is significantly (P0.01) lower in Kvß₁^–/– (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 I_K,slow density is significantly (P0.01) higher in Kvß₁^–/– (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 I_K,slow, I_K,slow2, is selectively increased in Kvß₁^–/– LVA myocytes. In parallel with the alterations in I_to,f and I_K,slow2 densities, Kv4.3 expression is decreased and Kv2.1 expression is increased in Kvß₁^–/– ventricles. Taken together, these results demonstrate that Kvß₁ differentially regulates the functional cell surface expression of myocardial I_to,f and I_K,slow2 channels.

Key Words: potassium channels • Kv accessory subunits • Kvß • I_to,f • I_K,slow

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