title: Differential autocrine modulation of atrial and ventricular potassium currents and of oxidative stress in diabetic rats.
abstract: 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 muM, >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.
authors.affiliation: Department of Physiology and Biophysics, Health Sciences Centre, University of Calgary, Alberta, Canada T2N 4N1. shimoni@ucalgary.ca
authors.forename: Yakhin
authors.initials: Y
authors.lastname: Shimoni
authors.forename: Don
authors.initials: D
authors.lastname: Hunt
authors.forename: Keyun
authors.initials: K
authors.lastname: Chen
authors.forename: Teresa
authors.initials: T
authors.lastname: Emmett
authors.forename: Gary
authors.initials: G
authors.lastname: Kargacin
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D015640:Ion Channel Gating; D008297:Male; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D013311:Streptozocin
chemical_list: D015221:Potassium Channels; D013311:Streptozocin; D011188:Potassium