PMID- 10414305
OWN - NLM
STAT- MEDLINE
DCOM- 19990812
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 868
DP  - 1999 Apr 30
TI  - The eag family of K+ channels in Drosophila and mammals.
PG  - 356-69
AB  - Mutations of eag, first identified in Drosophila on the basis of their
      leg-shaking phenotype, cause repetitive firing and enhanced transmitter release
      in motor neurons. The encoded EAG polypeptide is related both to voltage-gated K+
      channels and to cyclic nucleotide-gated cation channels. Homology screens
      identified a family of eag-related channel polypeptides, highly conserved from
      nematodes to humans, comprising three subfamilies: EAG, ELK, and ERG. When
      expressed in frog oocytes, EAG channels behave as voltage-dependent, outwardly
      rectifying K(+)-selective channels. Mutations of the human eag-related gene
      (HERG) result in a form of cardiac arrhythmia that can lead to ventricular
      fibrillation and sudden death. Electrophysiological and pharmacological studies
      have provided evidence that HERG channels specify one component of the delayed
      rectifier, IKr, that contributes to the repolarization phase of cardiac action
      potentials. An important role for HERG channels in neuronal excitability is also 
      suggested by the expression of these channels in brain tissue. Moreover,
      mutations of ERG-type channels in the Drosophila sei mutant cause
      temperature-induced convulsive seizures associated with aberrant bursting
      activity in the flight motor pathway. The in vivo function of ELK channels has
      not yet been established, but when these channels are expressed in frog oocytes, 
      they display properties intermediate between those of EAG- and ERG-type channels.
      Coexpression of the K(+)-channel beta subunit encoded by Hk with EAG in oocytes
      dramatically increases current amplitude and also affects the gating and
      modulation of these currents. Biochemical evidence indicates a direct physical
      interaction between EAG and HK proteins. Overall, these studies highlight the
      diverse properties of the eag family of K+ channels, which are likely to subserve
      diverse functions in vivo.
FAU - Ganetzky, B
AU  - Ganetzky B
AD  - Laboratory of Genetics, University of Wisconsin, Madison 53706, USA.
      ganetzky@facstaff.wisc.edu
FAU - Robertson, G A
AU  - Robertson GA
FAU - Wilson, G F
AU  - Wilson GF
FAU - Trudeau, M C
AU  - Trudeau MC
FAU - Titus, S A
AU  - Titus SA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Cation Transport Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (ERG protein, human)
RN  - 0 (ERG1 Potassium Channel)
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (Hk (hyperkinetic) protein, Drosophila)
RN  - 0 (KCNH2 protein, human)
RN  - 0 (KCNH6 protein, human)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcriptional Regulator ERG)
RN  - 0 (eag protein, Drosophila)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, EphB4)
RN  - EC 2.7.10.1 (Receptors, Eph Family)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arrhythmias, Cardiac/genetics
MH  - *Cation Transport Proteins
MH  - *DNA-Binding Proteins
MH  - Drosophila/*genetics/metabolism
MH  - Drosophila Proteins
MH  - ERG1 Potassium Channel
MH  - Electrophysiology
MH  - Ether-A-Go-Go Potassium Channels
MH  - Evolution, Molecular
MH  - Gene Expression Regulation
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Potassium Channels/*genetics/metabolism
MH  - *Potassium Channels, Voltage-Gated
MH  - Receptor Protein-Tyrosine Kinases/genetics
MH  - Receptor, EphB4
MH  - Receptors, Eph Family
MH  - Sequence Alignment
MH  - *Trans-Activators
MH  - Transcriptional Regulator ERG
EDAT- 1999/07/22 00:00
MHDA- 1999/07/22 00:01
CRDT- 1999/07/22 00:00
PHST- 1999/07/22 00:00 [pubmed]
PHST- 1999/07/22 00:01 [medline]
PHST- 1999/07/22 00:00 [entrez]
AID - 10.1111/j.1749-6632.1999.tb11297.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 1999 Apr 30;868:356-69. doi:
      10.1111/j.1749-6632.1999.tb11297.x.