Journal article
The transient outward current in mice lacking the potassium channel gene Kv1.4
The Journal of physiology, Vol.509(Pt 1), pp.171-182
05/15/1998
DOI: 10.1111/j.1469-7793.1998.171bo.x
PMCID: PMC2230931
PMID: 9547391
Abstract
The transient outward current (
I
to
) plays a prominent role in the repolarization phase of the cardiac action potential. Several K
+
channel genes, including
Kv1.4
, are expressed in the heart, produce rapidly inactivating currents when heterologously expressed, and may be the molecular basis of
I
to
.
We engineered mice homozygous for a targeted disruption of the K
+
channel gene
Kv1.4
and compared
I
to
in wild-type (Kv1.4
+/+
), heterozygous (Kv1.4
+/-
) and homozygous ‘knockout’ (Kv1.4
−/−
) mice. Kv1.4 RNA was truncated in Kv1.4
−/−
mice and protein expression was absent.
Adult myocytes isolated from Kv1.4
+/+
, Kv1.4
+/−
and Kv1.4
−/−
mice had large rapidly inactivating outward currents. The peak current densities at 60 mV (normalized by cellular capacitance, in pA pF
−1
; means ± s.e.m.) were 53.8 ± 5.3, 45.3 ± 2.2 and 44.4 ± 2.8 in cells from Kv1.4
+/+
, Kv1.4
+/−
and Kv1.4
−/−
mice, respectively (
P
< 0.02 for Kv1.4
+/+
vs
. Kv1.4
−/−
). The steady-state values (800 ms after the voltage clamp step) were 30.9 ± 2.9, 26.9 ± 3.8 and 23.5 ± 2.2, respectively (
P
< 0.02 for Kv1.4
+/+
vs
. Kv1.4
−/−
). The inactivating portion of the current was unchanged in the targeted mice.
The voltage dependence and time course of inactivation were not changed by targeted disruption of
Kv1.4
. The mean best-fitting
V
½
(membrane potential at 50 % inactivation) values for myocytes from Kv1.4
+/+
, Kv1.4
+/−
and Kv1.4
−/−
mice were -53.5 ± 3.7, -51.1 ± 2.6 and -54.2 ± 2.4 mV, respectively. The slope factors (
k
) were -10.1 ± 1.4, -8.8 ± 1.4 and -9.5 ± 1.2 mV, respectively. The fast time constants for development of inactivation at -30 mV were 27.8 ± 2.2, 26.2 ± 5.1 and 19.6 ± 2.1 ms in Kv1.4
+/+
, Kv1.4
+/−
and Kv1.4
−/−
myocytes, respectively. At +30 mV, they were 35.5 ± 2.6, 30.0 ± 2.1 and 28.7 ± 1.6 ms, respectively. The time constants for the rapid phase of recovery from inactivation at -80 mV were 32.5 ± 8.2, 23.3 ± 1.8 and 39.0 ± 3.7 ms, respectively.
Nearly the entire inactivating component as well as more than 60 % of the steady-state outward current was eliminated by 1 m
m
4-aminopyridine in Kv1.4
+/+
, Kv1.4
+/−
and Kv1.4
−/−
myocytes.
Western blot analysis of heart membrane extracts showed no significant upregulation of the Kv4 subfamily of channels in the targeted mice.
Thus, Kv1.4 is not the molecular basis of
I
to
in adult murine ventricular myocytes.
Details
- Title: Subtitle
- The transient outward current in mice lacking the potassium channel gene Kv1.4
- Creators
- Barry LondonDao W WangJoseph A HillPaul B Bennett
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.509(Pt 1), pp.171-182
- DOI
- 10.1111/j.1469-7793.1998.171bo.x
- PMID
- 9547391
- PMCID
- PMC2230931
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Publisher
- Blackwell Science Inc
- Language
- English
- Date published
- 05/15/1998
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025331002771
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