title: Novel effects of extracts from poisonous mushrooms on expression and function of the human ether-a-go-go-related gene channel.
abstract: The human ether-a-go-go-related gene (hERG) encodes the α subunit of the potassium current I(Kr), which plays a pivotal role in cardiac action potential repolarization. Inherited mutations of this gene cause Long QT syndrome type 2. hERG expression is altered by several types of drugs as well as by temperature. Heat shock protein 70 (Hsp70) and Heat shock cognate protein 70 (Hsc70) have reciprocal effects on hERG proteins. We examined the effects of poisonous mushrooms on hERG protein expression and its channel function.
  
  
  METHODS
  We evaluated the effects of several types of poisonous mushrooms on the expression and function of wild-type hERG by Western blotting, reverse transcription polymerase chain reaction (PCR), and patch clamping in transfected HEK293 cells and mouse HL-1 cardiomyocytes.
  
  
  RESULTS
  Extracts of Gymnopilus junonius (junonius) increased expression of both hERG and Hsp70 in HEK293 cells with concomitant decrease in Hsc70, whereas extracts of Amanita ibotengutake (ibotengutake) decreased hERG proteins with increase in Hsc70. Knockdown of Hsp70 and Hsc70 by small interfering RNA abolished the effects of the two mushrooms on hERG, respectively. Certain fractions of junonius increased expression of hERG proteins. hERG currents were increased by extracts of junonius, resulting in shortening of action potential duration (APD). In contrast, hERG currents were decreased and APD was prolonged by extracts of ibotengutake.
  
  
  CONCLUSIONS
  junonius enhanced the expression and function of hERG by increasing Hsp70 and decreasing Hsc70. Ibotengutake decreased hERG expression via increase in Hsc70. Constituents of junonius may have the potential for use in treatment of arrhythmia.
authors: Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University, Japan.
authors: Peili
authors: P
authors: Li
authors: Saki
authors: S
authors: Tanaka
authors: Tsuyoshi
authors: T
authors: Ichiyanagi
authors: Haruaki
authors: H
authors: Ninomiya
authors: Yakuang
authors: Y
authors: Ting
authors: Sulistiyati-Bayu
authors: SB
authors: Utami
authors: Tadanori
authors: T
authors: Aimi
authors: Yasuaki
authors: Y
authors: Shirayoshi
authors: Junichiro
authors: J
authors: Miake
authors: Ichiro
authors: I
authors: Hisatome
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000363:Agaricales; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D051638:Ether-A-Go-Go Potassium Channels; D018840:HSP70 Heat-Shock Proteins; D034741:RNA, Small Interfering