Developmental evolution of the delayed rectifier current IKs in canine heart appears dependent on the beta subunit minK.
OBJECTIVE
We tested the hypothesis that the developmental changes occurring in I(Kr) and I(Ks) can be explained by changes in the expression of ERG encoding I(Kr), and KCNQ1, the beta subunit minK, and the recently reported subunit FHL2 encoding I(Ks).


BACKGROUND
The delayed rectifier current contributes importantly to the developmental evolution of the canine myocardial action potential. Specifically, in left ventricular epicardial myocytes, I(Ks) is absent and I(Kr) is the major repolarizing current until age 4 weeks. With subsequent development, I(Ks) density increases and I(Kr) decreases, resulting in an altered voltage-time course of repolarization.


METHODS
We used Western blotting and real-time polymerase chain reaction to compare the expression of ERG, KCNQ1, minK, and FHL2 in 1-week-old pups and adult dogs.


RESULTS
ERG levels are high at 1 week and decrease significantly with age, consistent with developmental decrease in I(Kr). Whereas expression of KCNQ1 and FHL2 is unchanged between the two age groups, minK is minimally expressed at 1 week and increases in adults, consistent with developmental increase in I(Ks).


CONCLUSIONS
A reduction in ERG explains the developmental decrease in I(Kr), whereas the accessory subunit minK appears to be the critical determinant of developmental evolution of I(Ks).
Krishnamurthy
Ganga
G
Department of Pharmacology, Center for Molecular Therapeutics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Patberg
Kornelis W
KW
Obreztchikova
Maria N
MN
Rybin
Andrew V
AV
Rosen
Michael R
MR
D000375:Aging / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000378:metabolism*; D004285:Dogs; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism*; D010496:Pericardium / Q000166:cytology; D016133:Polymerase Chain Reaction; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger