Gender-dependent attenuation of cardiac potassium currents in type 2 diabetic
db/db mice.
Authors Shimoni Y, Chuang M, Abel ED, Severson DL.
Submitted By E. Dale Abel on 3/3/2004
Status Published
Journal The Journal of physiology
Year 2003
Date Published 3/1/2004
Volume : Pages 555 : 345 - 354
PubMed Reference 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 microm, 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.

Investigators with authorship
E. Dale AbelUniversity of Iowa