Characterization of a voltage-gated K+ channel beta subunit expressed in human heart.
Voltage-gated K+ channels are important modulators of the cardiac action potential. However, the correlation of endogenous myocyte currents with K+ channels cloned from human heart is complicated by the possibility that heterotetrameric alpha-subunit combinations and function-altering beta subunits exist in native tissue. Therefore, a variety of subunit interactions may generate cardiac K+ channel diversity. We report here the cloning of a voltage-gated K+ channel beta subunit, hKv beta 3, from adult human left ventricle that shows 84% and 74% amino acid sequence identity with the previously cloned rat Kv beta 1 and Kv beta 2 subunits, respectively. Together these three Kv beta subunits share > 82% identity in the carboxyl-terminal 329 aa and show low identity in the amino-terminal 79 aa. RNA analysis indicated that hKv beta 3 message is 2-fold more abundant in human ventricle than in atrium and is expressed in both healthy and diseased human hearts. Coinjection of hKv beta 3 with a human cardiac delayed rectifier, hKv1.5, in Xenopus oocytes increased inactivation, induced an 18-mV hyperpolarizing shift in the activation curve, and slowed deactivation (tau = 8.0 msec vs. 35.4 msec at -50 mV). hKv beta 3 was localized to human chromosome 3 by using a human/rodent cell hybrid mapping panel. These data confirm the presence of functionally important K+ channel beta subunits in human heart and indicate that beta-subunit composition must be accounted for when comparing cloned channels with endogenous cardiac currents.
England
S K
SK
Department of Molecular Physiology, Vanderbilt University of Medicine, Nashville, TN 37232, USA.
Uebele
V N
VN
Shear
H
H
Kodali
J
J
Bennett
P B
PB
Tamkun
M M
MM
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D017124:Conserved Sequence; D017931:DNA Primers; D018076:DNA, Complementary / Q000302:isolation & purification / Q000378:metabolism; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D006352:Heart Ventricles; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D012016:Reference Values; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D018076:DNA, Complementary; D046911:Macromolecular Substances; D015221:Potassium Channels; D012333:RNA, Messenger