Journal article
Gender-dependent attenuation of cardiac potassium currents in type 2 diabetic db/db mice
The Journal of physiology, Vol.555(Pt 2), pp.345-354
03/01/2004
DOI: 10.1113/jphysiol.2003.055590
PMCID: PMC1664833
PMID: 14694146
Abstract
Single ventricular myocytes were prepared from control
db
/+ and insulin-resistant diabetic
db/db
male mice at 6 and 12 weeks of age. Peak and sustained outward potassium currents were measured using whole-cell voltage clamp methods. At 6 weeks currents were fully developed in control and diabetic mice, with no differences in the density of either current. By 12 weeks both currents were significantly attenuated in the diabetic mice, but could be augmented by
in vitro
incubation with the angiotensin-converting enzyme (ACE) inhibitor quinapril (1 μ
m
, 5–9 h). In cells from female
db/db
mice (12 weeks of age), K
+
currents were not attenuated and no effects of quinapril were observed. To investigate whether lack of insulin action accounts for these gender differences, cells were also isolated from cardiomyocte-specific insulin receptor knockout (CIRKO) mice. Both K
+
currents were significantly attenuated in cells from male and female CIRKO mice, and action potentials were significantly prolonged. Incubation with quinapril did not augment K
+
currents. Our results demonstrate that type 2 diabetes is associated with gender-selective attenuation of K
+
currents in cardiomyocytes, which may underlie gender differences in the development of some cardiac arrhythmias. The mechanism for attenuation of K
+
currents in cells from male mice is due, at least in part, to an autocrine effect resulting from activation of a cardiac renin–angiotensin system. Insulin is not involved in these gender differences, since the absence of insulin action in CIRKO mice diminishes K
+
currents in cells from both males and females.
Details
- Title: Subtitle
- Gender-dependent attenuation of cardiac potassium currents in type 2 diabetic db/db mice
- Creators
- Yakhin ShimoniMariette ChuangE Dale AbelDavid L Severson
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.555(Pt 2), pp.345-354
- DOI
- 10.1113/jphysiol.2003.055590
- PMID
- 14694146
- PMCID
- PMC1664833
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Publisher
- Blackwell Science Inc
- Language
- English
- Date published
- 03/01/2004
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024502302771
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