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AKAP proteins anchor cAMP-dependent protein kinase to KvLQT1/IsK channel complex
Ist Teil von
American journal of physiology. Heart and circulatory physiology, 2001-05, Vol.280 (5), p.H2038-H2045
Ort / Verlag
United States
Erscheinungsjahr
2001
Quelle
MEDLINE
Beschreibungen/Notizen
1 Laboratoire de Physiopathologie et de Pharmacologie
Cellulaires et Moléculaires, Hôpital Hôtel-Dieu,
Institut National de la Santé et de la Recherche Médicale,
44093 Nantes Cedex, France; and 2 Howard Hughes Medical
Institute, Vollum Institute, Portland, Oregon 97201
In cardiac myocytes, the slow component of the
delayed rectifier K + current ( I Ks )
is regulated by cAMP. Elevated cAMP increases
I Ks amplitude, slows its deactivation kinetics,
and shifts its activation curve. At the molecular level,
I Ks 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 I Ks 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 I Ks 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
I Ks requires protein kinase A anchoring by
AKAPs, which therefore participate with the channel protein complex
underlying I Ks .
A kinase anchoring protein; KCNQ1 ; KCNE1 ; slow delayed rectifier potassium current