Journal article
Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes
The Journal of physiology, Vol.521(Pt 3), pp.587-599
12/15/1999
DOI: 10.1111/j.1469-7793.1999.00587.x
PMCID: PMC2269690
PMID: 10601491
Abstract
Two kinetically and pharmacologically distinct transient outward K
+
currents, referred to as
I
to,f
and
I
to,s
, have been distinguished in mouse left ventricular myocytes.
I
to,f
is present in all left ventricular apex cells and in most left ventricular septum cells, whereas
I
to,s
is identified exclusively in left ventricular septum cells.
Electrophysiological recordings from ventricular myocytes isolated from animals with a targeted deletion of the
Kv1.4
gene (Kv1.4
−/−
mice) reveal that
I
to,s
is undetectable in cells isolated from the left ventricular septum (
n
= 26).
I
to,f
density in both apex and septum cells, in contrast, is not affected by deletion of
Kv1.4.
Neither the 4-AP-sensitive, slowly inactivating K
+
current,
I
K,slow
, nor the steady-state non-inactivating K
+
current,
I
SS
, is affected in Kv1.4
−/−
mouse left ventricular cells.
In myocytes isolated from transgenic mice expressing a dominant negative Kv4.2 α subunit, Kv4.2W362F,
I
to,f
is eliminated in both left ventricular apex and septum cells. In addition, a slowly inactivating transient outward K
+
current similar to
I
to,s
in wild-type septum cells is evident in myocytes isolated from left ventricular apex of Kv4.2W362F-expressing transgenics. The density of
I
to,s
in septum cells, however, is unaffected by Kv4.2W362F expression.
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 α subunits, Kv1.2 and Kv2.1, in contrast, are not affected by the expression of the Kv4.2W362F transgene.
The results presented here demonstrate that the molecular correlates of
I
to,f
and
I
to,s
in adult mouse ventricle are distinct. Kv1.4 underlies mouse ventricular septum
I
to,s
, whereas Kv α subunits of the Kv4 subfamily underlie mouse ventricular apex and septum
I
to,f
. The appearance of the slow transient outward K
+
current in Kv4.2W362F-expressing left ventricular apex cells with properties indistinguishable from
I
to,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.
Details
- Title: Subtitle
- Molecular basis of transient outward K+ current diversity in mouse ventricular myocytes
- Creators
- Weinong GuoHaodong XuBarry LondonJeanne M Nerbonne
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.521(Pt 3), pp.587-599
- DOI
- 10.1111/j.1469-7793.1999.00587.x
- PMID
- 10601491
- PMCID
- PMC2269690
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Publisher
- Blackwell Science Inc
- Language
- English
- Date published
- 12/15/1999
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025404702771
Metrics
18 Record Views