title: Sex differences in the modulation of K+ currents in diabetic rat cardiac myocytes.
abstract: A transient (Ipeak) and a sustained (Isus) outward K+ current were measured, using whole-cell voltage-clamp methods, in isolated rat ventricular myocytes obtained by enzymatic dispersion. A comparison was made between male and female rats following induction of (insulin-deficient) diabetes with streptozotocin (STZ). In control (non-diabetic) rats, both currents were smaller in cells obtained from females, as compared to males (P<0.005). However, whereas inducing diabetes in male rats significantly attenuated both Ipeak and Isus (P<0.005), Ipeak was unchanged in female diabetic rats. Isus was significantly (P<0.005) reduced, but the extent of reduction was smaller (P<0.02) than in males. The formation of angiotensin II (ATII) or endothelin-1 (ET-1) was blocked using inhibitors of angiotensin-converting enzyme (ACE) and endothelin-converting enzyme (ECE), respectively. In cells from diabetic males both inhibitors significantly (P<0.005) enhanced K+ currents. In contrast, no effect was observed in cells from female diabetic rats. However, in ovariectomized (Ovx) diabetic females the in vitro inhibition of ATII and ET-1 formation augmented the two K+ currents, but not when oestradiol was administered in vivo prior to cell isolation. In cells from diabetic males, incubation with 100 nM 17beta-oestradiol significantly (P<0.005) enhanced both Ipeak and Isus. This effect was blocked if ATII or ET-1 was added to the medium. These results show that autocrine modulation of K+ currents by renin-angiotensin and endothelin systems is attenuated or absent in female diabetic rats. Oestradiol plays a key role in reducing this modulation. These results may underlie some of the sex differences associated with development of cardiac arrhythmias.
authors.affiliation: Cardiovascular Research Group, Department of Physiology and Biophysics, University of Calgary, Alberta, Canada T2N 4N1. shimoni@ucalgary.ca
authors.forename: Yakhin
authors.initials: Y
authors.lastname: Shimoni
authors.forename: Xiu-Fang
authors.initials: XF
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019332:Endothelin-1; D015221:Potassium Channels; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D004958:Estradiol; D000077583:Quinapril