Journal
CIRCULATION RESEARCH
Volume 96, Issue 4, Pages 451-458Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000156890.25876.63
Keywords
potassium channels; Kv accessory subunits; Kv beta; I-to,I-f; I-K,I-slow
Funding
- NHLBI NIH HHS [HL-066388, HL-034161] Funding Source: Medline
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Voltage-gated K+ (Kv) channel accessory (beta) subunits associate with pore-forming Kv alpha 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 beta subunits in the generation of native cardiac Kv channels. Exploiting mice with a targeted disruption of the Kvbeta(1) gene (Kvbeta(1)(-/-)), the studies here were undertaken to explore directly the role of Kvbeta(1) 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 Kvbeta(1)(-/-) and wild-type (WT) animals. Analysis of Kv current waveforms, however, revealed that mean+/-SEM I-to,I-f density is significantly (Pless than or equal to0.01) lower in Kvbeta(1)(-/-) (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,I-slow density is significantly (Pless than or equal to0.01) higher in Kvbeta(1)(-/-) (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,I-slow, I-K,I-slow2, is selectively increased in Kvbeta(1)(-/-) LVA myocytes. In parallel with the alterations in I-to,I-f and I-K,I-slow2 densities, Kv4.3 expression is decreased and Kv2.1 expression is increased in Kvbeta(1)(-/-) ventricles. Taken together, these results demonstrate that Kvbeta(1) differentially regulates the functional cell surface expression of myocardial I-to,I-f and I-K,I-slow2 channels.
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