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Sex differences in the modulation of K + currents in diabetic rat cardiac myocytes
Author(s) -
Shimoni Yakhin,
Liu XiuFang
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2003.041269
Subject(s) - endocrinology , medicine , ovariectomized rat , endothelin 1 , diabetes mellitus , streptozotocin , angiotensin ii , myocyte , renin–angiotensin system , endothelin receptor , in vivo , angiotensin converting enzyme , chemistry , hormone , biology , receptor , microbiology and biotechnology , blood pressure
A transient ( I peak ) and a sustained ( I sus ) 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 I peak and I sus ( P < 0.005 ), I peak was unchanged in female diabetic rats. I sus 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 17β‐oestradiol significantly ( P < 0.005 ) enhanced both I peak and I sus . 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.