AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1/IsK channel complex

Franck Potet, John D. Scott, Raha Mohammad-Panah, Denis Escande*, Isabelle Baró

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

In cardiac myocytes, the slow component of the delayed rectifier K+ current (IKs) is regulated by cAMP. Elevated cAMP increases IKs amplitude, slows its deactivation kinetics, and shifts its activation curve. At the molecular level, IKs channels are composed of KvLQT1/IsK complexes. In a variety of mammalian heterologous expression systems maintained at physiological temperature, we explored cAMP regulation of recombinant KvLQT1/IsK complexes. In these systems, KvLQT1/IsK complexes were totally insensitive to cAMP regulation. cAMP regulation was not restored by coexpression with the dominant negative isoform of KvLQT1 or with the cystic fibrosis transmembrane regulator. In contrast, coexpression of the neuronal A kinase anchoring protein (AKAP)79, a fragment of a cardiac AKAP (mAKAP), or cardiac AKAP15/18 restored cAMP regulation of KvLQT1/IsK complexes inasmuch as cAMP stimulation increased the/IKs amplitude, increased its deactivation time constant, and negatively shifted its activation curve. However, in cells expressing an AKAP, the effects of cAMP stimulation on the IKs amplitude remained modest compared with those previously reported in cardiac myocytes. The effects of cAMP stimulation were fully prevented by including the Ht31 peptide (a global disruptor of protein kinase A anchoring) in the intracellular medium. We concluded that cAMP regulation of IKs requires protein kinase A anchoring by AKAPs, which therefore participate with the channel protein complex underlying IKs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number5 49-5
StatePublished - May 1 2001

Keywords

  • A kinase anchoring protein
  • KCNE1
  • KCNQ1
  • Slow delayed rectifier potassium current

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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