Article

alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells.

Department of Physiology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada.
FEBS Letters (impact factor: 3.54). 06/2000; 473(2):188-94. pp.188-94
Source: PubMed

ABSTRACT Voltage-gated K(+) (Kv) channels are particularly important in the physiology of excitable cells in the heart and the brain. PSD-95 is known to cluster Shaker channels and NMDA receptors and the latter is known to couple through alpha-actinin-2 to the post-synaptic cytoskeleton [Wyszynski et al. (1997) Nature 385, 439-442], but the mechanisms by which Kv channels are linked to the actin cytoskeleton and clustered at specific sites in the heart are unknown. Here we provide evidence that Kv1.5 channels, widely expressed in the cardiovascular system, bind with alpha-actinin-2. Human Kv1.5 interacts via its N-terminus/core region and can be immunoprecipitated with alpha-actinin-2 both after in vitro translation and from HEK cells expressing both proteins. The ion channels and alpha-actinin-2 co-localize at the membrane in HEK cells, where disruption of the actin cytoskeleton and antisense constructs to alpha-actinin-2 modulate the ion and gating current density.

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Keywords

actin cytoskeleton
 
alpha-actinin-2
 
alpha-actinin-2 co-localize
 
alpha-actinin-2 modulate
 
antisense constructs
 
bind
 
cluster Shaker channels
 
disruption
 
excitable cells
 
gating current density
 
HEK cells
 
Human Kv1.5 interacts
 
Kv1.5 channels
 
physiology
 
post-synaptic cytoskeleton [Wyszynski
 
specific sites
 
vitro translation
 
Voltage-gated K(+)