Accessory Kvβ1 Subunits Differentially Modulate the Functional Expression of Voltage-Gated K+ Channels in Mouse Ventricular Myocytes

• Published in: Circulation research 2005-03, Vol.96 (4), p.451-458
• Main Authors: Aimond, Franck, Kwak, Seung P, Rhodes, Kenneth J, Nerbonne, Jeanne M
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.0000156890.25876.63

Voltage-gated K (Kv) channel accessory (β) subunits associate with pore-forming Kv α 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 β subunits in the generation of native cardiac Kv channels. Exploiting mice with a targeted disruption of the Kvβ1 gene (Kvβ1), the studies here were undertaken to explore directly the role of Kvβ1 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 Kvβ1 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 Kvβ1 (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 (P≤0.01) higher in Kvβ1 (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 Kvβ1 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 Kvβ1 ventricles. Taken together, these results demonstrate that Kvβ1 differentially regulates the functional cell surface expression of myocardial Ito,f and IK,slow2 channels.