Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system.

@article{Kupershmidt1999ReplacementBH,
  title={Replacement by homologous recombination of the minK gene with lacZ reveals restriction of minK expression to the mouse cardiac conduction system.},
  author={Sabina Kupershmidt and T. Yang and M. E. Anderson and Andy Wessels and Kevin D. Niswender and Mark A. Magnuson and Dan M. Roden},
  journal={Circulation research},
  year={1999},
  volume={84 2},
  pages={
          146-52
        }
}
The minK gene encodes a 129-amino acid peptide the expression of which modulates function of cardiac delayed rectifier currents (IKr and IKs), and mutations in minK are now recognized as one cause of the congenital long-QT syndrome. We have generated minK-deficient mice in which the bacterial lacZ gene has been substituted for the minK coding region such that beta-galactosidase expression is controlled by endogenous minK regulatory elements. In cardiac myocytes isolated from wild-type neonatal… 

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References

SHOWING 1-10 OF 43 REFERENCES

Coassembly of KVLQT1 and minK (IsK) proteins to form cardiac IKS potassium channel

TLDR
KVLQT1 is the subunit that coassembles with minK to form IKS channels and IKS dysfunction is a cause of cardiac arrhythmia, and is shown to encode a K+ channel with biophysical properties unlike other known cardiac currents.

Anti-minK antisense decreases the amplitude of the rapidly activating cardiac delayed rectifier K+ current.

TLDR
The rapidly and slowly activating delayed rectifier K+ currents (IKr and IKs, respectively), which have different physiological properties have been identified in cardiac cells from several species, including humans, and the role of this gene product in channel function remains controversial.

KvLQT1 and IsK (minK) proteins associate to form the IKS cardiac potassium current

TLDR
It is shown that KVLQT1 associates with IsK to form the channel underlying the IKS cardiac current, which is a target of class-Ill anti-arrhythmic drugs and is involved in the L QT1 syndrome.

Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current.

TLDR
A novel N-terminal Erg isoform is identified that is expressed specifically in the heart, has rapid deactivation kinetics, and coassembles with the longer isoform in Xenopus oocytes.

Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.

TLDR
K(V)LQT1 is the subunit that coassembles with minK to form I(Ks) channels and I( Ks) dysfunction is a cause of cardiac arrhythmia.

Expression of a minimal K+ channel protein in mammalian cells and immunolocalization in guinea pig heart.

TLDR
The first expression of minK activity in transiently transfected mammalian (HEK 293) cells is reported and it is demonstrated that the characteristics of the expressed minK current are similar to those of IKs recorded from guinea pig heart cells under similar experimental conditions, providing strong evidence that a minK-like protein underlies Iks.

A minK–HERG complex regulates the cardiac potassium current IKr

TLDR
It is shown that HERG and minK form a stable complex, and that this heteromultimerization regulates IKr activity, which is central to the control of the heart rate and rhythm.

Involvement of IsK-associated K+ channel in heart rate control of repolarization in a murine engineered model of Jervell and Lange-Nielsen syndrome.

TLDR
It is concluded that the isk gene product and/or ISKs, when present, blunts the QT adaptation to heart rate variations and that steeper QT-RR relationships reflect a greater susceptibility to arrhythmias in patients lacking IKs.

Electrophysiological characterization of an alternatively processed ERG K+ channel in mouse and human hearts.

TLDR
ERG B, an alternatively processed isoform of the ERG gene, expressed selectively in heart and with electrophysiological characteristics similar to those of native cardiac IKr is identified.

Cloning, expression, pharmacology and regulation of a delayed rectifier K+ channel in mouse heart.

TLDR
Cultured newborn mouse ventricular cardiac cells exhibited a delayed rectifier K+ current which had biophysical properties similar to those of cloned mIsK and which was inhibited by clofilium and protein kinase C activators.