title: Circadian variation of cardiac K+ channel gene expression.
abstract: BACKGROUND
  Many cardiac arrhythmias have their own characteristic circadian variations. Because the expression of many genes, including clock genes, is regulated variably during a day, circadian variations of ion channel gene expression, if any, could contribute to the fluctuating alterations of cardiac electrophysiological characteristics and subsequent arrhythmogenesis.
  
  
  RESULTS
  To examine whether cardiac K+ channel gene expression shows a circadian rhythm, we analyzed the mRNA levels of 8 Kv and 6 Kir channels in rat hearts every 3 hours throughout 1 day. Among these channels, Kv1.5 and Kv4.2 genes showed significant circadian variations in their transcripts: approximately 2-fold increase of Kv1.5 mRNA from trough at Zeitgeber time (ZT) 6 to peak at ZT18 and a completely reverse pattern in Kv4.2 mRNA ( approximately 2-fold increase from trough at ZT18 to peak at ZT6). Actually, along with the variations in the immunoreactive proteins, the density of the transient outward and steady-state currents in isolated myocytes and the responses of atrial and ventricular refractoriness to 4-aminopyridine in isolated-perfused hearts showed differences between ZT6 and ZT18, a circadian pattern comparable to that of Kv1.5 and Kv4.2 gene expression. Reversal of light stimulation almost inverted these circadian rhythms, although pharmacological autonomic blockade only partially attenuated the rhythm of Kv1.5 but not of Kv4.2 transcripts.
  
  
  CONCLUSIONS
  Among all the cardiac K+ channels, Kv1.5 and 4.2 channels are unique in showing characteristic circadian patterns in their gene expression, with Kv1.5 increase during the dark period partially dependent on beta-adrenergic activities and Kv4.2 increase during the light period independent of the autonomic nervous function.
authors.affiliation: The Cardiovascular Institute, Roppongi 7-3-10, Minato-ku, Tokyo 106-0032, Japan. yamt-tky@umin.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Akiko
authors.initials: A
authors.lastname: Sekiguchi
authors.forename: Yu-ki
authors.initials: YK
authors.lastname: Iwasaki
authors.forename: Kouichi
authors.initials: K
authors.lastname: Sagara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Iinuma
authors.forename: Seiji
authors.initials: S
authors.lastname: Hatano
authors.forename: Long-Tai
authors.initials: LT
authors.lastname: Fu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002940:Circadian Rhythm; D004553:Electric Conductivity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006321:Heart / Q000502:physiology; D051666:Kv1.5 Potassium Channel; D008027:Light; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels
chemical_list: D000319:Adrenergic beta-Antagonists; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D011433:Propranolol