PMID- 10601491
OWN - NLM
STAT- MEDLINE
DCOM- 20000821
LR  - 20190513
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 521 Pt 3
DP  - 1999 Dec 15
TI  - Molecular basis of transient outward K+ current diversity in mouse ventricular
      myocytes.
PG  - 587-99
AB  - 1. Two kinetically and pharmacologically distinct transient outward K+ currents, 
      referred to as Ito,f and Ito,s, have been distinguished in mouse left ventricular
      myocytes. Ito,f is present in all left ventricular apex cells and in most left
      ventricular septum cells, whereas Ito,s is identified exclusively in left
      ventricular septum cells. 2. Electrophysiological recordings from ventricular
      myocytes isolated from animals with a targeted deletion of the Kv1.4 gene
      (Kv1.4-/- mice) reveal that Ito,s is undetectable in cells isolated from the left
      ventricular septum (n = 26). Ito,f density in both apex and septum cells, in
      contrast, is not affected by deletion of Kv1.4. 3. Neither the 4-AP-sensitive,
      slowly inactivating K+ current, IK,slow, nor the steady-state non-inactivating K+
      current, ISS, is affected in Kv1.4-/- mouse left ventricular cells. 4. In
      myocytes isolated from transgenic mice expressing a dominant negative Kv4.2 alpha
      subunit, Kv4.2W362F, Ito,f is eliminated in both left ventricular apex and septum
      cells. In addition, a slowly inactivating transient outward K+ current similar to
      Ito,s in wild-type septum cells is evident in myocytes isolated from left
      ventricular apex of Kv4.2W362F-expressing transgenics. The density of Ito,s in
      septum cells, however, is unaffected by Kv4.2W362F expression. 5. Western blots
      of fractionated mouse ventricular membrane proteins reveal a significant increase
      in Kv1.4 protein level in Kv4.2W362F-expressing transgenic mice. The protein
      levels of other Kv alpha subunits, Kv1.2 and Kv2.1, in contrast, are not affected
      by the expression of the Kv4.2W362F transgene. 6. The results presented here
      demonstrate that the molecular correlates of Ito,f and Ito,s in adult mouse
      ventricle are distinct. Kv1.4 underlies mouse ventricular septum Ito,s, whereas
      Kv alpha subunits of the Kv4 subfamily underlie mouse ventricular apex and septum
      Ito, f. The appearance of the slow transient outward K+ current in Kv4.
      2W362F-expressing left ventricular apex cells with properties indistinguishable
      from Ito,s in wild-type cells is accompanied by an increase in Kv1.4 protein
      expression, suggesting that the upregulation of Kv1.4 underlies the observed
      electrical remodeling in Kv4.2W362F-expressing transgenics.
FAU - Guo, W
AU  - Guo W
AD  - Department of Molecular Biology and Pharmacology, Washington University School of
      Medicine, St Louis, MO 63110, USA.
FAU - Xu, H
AU  - Xu H
FAU - London, B
AU  - London B
FAU - Nerbonne, J M
AU  - Nerbonne JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Kcna4 protein, mouse)
RN  - 0 (Kv1.4 Potassium Channel)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Voltage-Gated)
RN  - 0 (Shal Potassium Channels)
SB  - IM
MH  - Action Potentials/physiology
MH  - Algorithms
MH  - Animals
MH  - Blotting, Western
MH  - Electrophysiology
MH  - Heart Ventricles/cytology/metabolism
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Kv1.4 Potassium Channel
MH  - Membrane Potentials/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocardium/cytology/*metabolism
MH  - Patch-Clamp Techniques
MH  - Potassium Channels/chemistry/drug effects/genetics/*metabolism
MH  - *Potassium Channels, Voltage-Gated
MH  - Shal Potassium Channels
MH  - Up-Regulation/genetics/physiology
PMC - PMC2269690
EDAT- 1999/12/22 09:00
MHDA- 2000/08/29 11:01
CRDT- 1999/12/22 09:00
PHST- 1999/12/22 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 1999/12/22 09:00 [entrez]
AID - PHY_9707 [pii]
AID - 10.1111/j.1469-7793.1999.00587.x [doi]
PST - ppublish
SO  - J Physiol. 1999 Dec 15;521 Pt 3:587-99. doi: 10.1111/j.1469-7793.1999.00587.x.