The Journal of Neuroscience, December 1, 2002, 22(23):10123-10133


PKA Modulation of Kv4.2-Encoded A-Type Potassium Channels Requires Formation 
of a Supramolecular Complex 

Laura A. Schrader-1, Anne E. Anderson-1,2, Amber Mayne-1, Paul J. Pfaffinger-1, 
and John David Sweatt-1 

1 Division of Neuroscience and 2 Departments of Pediatrics and Neurology, 
Baylor College of Medicine, Houston, Texas 77030 


A-type channels, encoded by the pore-forming a-subunits of the Kv4.x family, 
are particularly important in regulating membrane excitability in the CNS and 
the heart. Given the key role of modulation of A currents by kinases, we sought 
to investigate the protein structure-function relationships underlying the 
regulation of these currents by PKA. We have previously shown the existence of 
two PKA phosphorylation sites in the Kv4.2 sequence; therefore, we focused this 
study on the Kv4.2 primary subunit. In the present studies we made the surprising 
finding that PKA phosphorylation of the Kv4.2 a-subunit is necessary but not 
sufficient for channel modulation; channel modulation by PKA required the presence 
of an ancillary subunit, the K+ channel interacting protein (KChIP3). Therefore, 
these findings indicate a surprising complexity to kinase regulation of A currents, 
in that an interaction of two separate molecular events, a-subunit phosphorylation 
and the association of an ancillary subunit (KChIP3), are necessary for 
phosphorylation-dependent regulation of Kv4.2-encoded A channels by PKA. Overall, 
our studies indicate that PKA must of necessity act on a supramolecular complex of 
pore-forming a-subunits plus ancillary subunits to alter channel properties. 


Key words: KChIP; phosphorylation; neuromodulation; Kv4.2; shal-type; PKA; 
heart; neuron 



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Copyright © 2002 Society for Neuroscience