Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks).
Voltage-gated potassium (K(V)) channels are modulated by at least three distinct classes of proteins including the KCNE family of single transmembrane accessory subunits. In the human genome, KCNE proteins are encoded by five genes designated KCNE1 through KCNE5. KCNE1 associates with KCNQ1 in vitro to generate a potassium current closely resembling the slowly activating delayed rectifier (I(Ks)). Other KCNE proteins also affect the activity of heterologously expressed KCNQ1. To investigate the potential physiological relevance of this gene family in human heart, we examined the relative expression of KCNQ1 and all five KCNE genes in samples derived from normal tissues representing major regions of human heart by real-time, quantitative RT-PCR. KCNE genes are expressed in human heart with a relative abundance ranking of KCNE1 > KCNE4 > KCNE5 approximately KCNE3 >> KCNE2. In situ hybridization revealed prominent expression of KCNE1 and KCNE3-5 in human atrial myocytes. In cardiomyopathic hearts, expression of KCNE1, KCNE3, KCNE4, and KCNQ1 was significantly increased, while KCNE2 and KCNE5 exhibited reduced expression. In a cell line stably expressing KCNQ1 and KCNE1, transient expression of KCNE3, KCNE4, or KCNE5 significantly altered I(Ks) current profiles. Even in the presence of additional KCNE1, KCNE4 and KCNE5 exert dominant effects on I(Ks). Although KCNE1 is the predominant KCNE family member expressed in human heart, the abundance of other KCNE transcripts including potential KCNQ1 suppressors (KCNE4 and KCNE5) and their altered expression patterns in disease lead us to speculate that a balance of KCNE accessory subunits may be important for cardiac K(V) channel function.
Lundquist
Andrew L
AL
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Manderfield
Lauren J
LJ
Vanoye
Carlos G
CG
Rogers
Christopher S
CS
Donahue
Brian S
BS
Chang
Paul A
PA
Drinkwater
Davis C
DC
Murray
Katherine T
KT
George
Alfred L
AL
D000328:Adult; D000368:Aged; D000818:Animals; D016466:CHO Cells; D009202:Cardiomyopathies / Q000235:genetics / Q000473:pathology; D006224:Cricetinae; D004594:Electrophysiology; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D017136:Ion Transport; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
C498897:KCNE4 protein, human; C502068:KCNE5 protein, human; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D012333:RNA, Messenger; D011188:Potassium