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Differential autocrine modulation of atrial and ventricular potassium currents and of oxidative stress in diabetic rats

Department of Physiology and Biophysics, Health Sciences Centre, University of Calgary, Alberta, Canada

Submitted 4 October 2005 ; accepted in final form 2 December 2005

The autocrine modulation of cardiac K⁺ currents was compared in ventricular and atrial cells (V and A cells, respectively) from Type 1 diabetic rats. K⁺ currents were measured by using whole cell voltage clamp. ANG II was measured by ELISA and immunofluorescent labeling. Oxidative stress was assessed by immunofluorescent labeling with dihydroethidium, a measure of superoxide ions. In V cells, K⁺ currents are attenuated after activation of the renin-angiotensin system (RAS) and the resulting ANG II-mediated oxidative stress. In striking contrast, these currents are not attenuated in A cells. Inhibition of the angiotensin-converting enzyme (ACE) also has no effect, in contrast to current augmentation in V cells. ANG II levels are enhanced in V, but not in A, cells. However, the high basal ANG II levels in A cells suggest that in these cells, ANG II-mediated pathways are suppressed, rather than ANG II formation. Concordantly, superoxide ion levels are lower in diabetic A than in V cells. Several findings indicate that high atrial natriuretic peptide (ANP) levels in A cells inhibit RAS activation. In male diabetic V cells, in vitro ANP (300 nM–1 µM, >5 h) decreases oxidative stress and augments K⁺ currents, but not when excess ANG II is present. ANP has no effect on ventricular K⁺ currents when the RAS is not activated, as in control males, in diabetic males treated with ACE inhibitor and in diabetic females. In conclusion, the modulation of K⁺ currents and oxidative stress is significantly different in A and V cells in diabetic rat hearts. The evidence suggests that this is largely due to inhibition of RAS activation and/or action by ANP in A cells. These results may underlie chamber-specific arrhythmogenic mechanisms.

diabetes; cardiac potassium currents

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