Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic stimulation in rabbits Journal Article

Local Library Link: Find It @ Loyola

Authors: Zhu, Y.; Ai, X; Oster, R. A.; Bers, D. M.; Pogwizd, S. M.
Article Title: Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic stimulation in rabbits
Abstract: Slow delayed rectifier potassium current (IKs) is important in action potential (AP) repolarization and repolarization reserve. We tested the hypothesis that there are sex-specific differences in IKs, AP, and their regulation by beta-adrenergic receptors (beta-AR's) using whole-cell patch-clamp. AP duration (APD90) was significantly longer in control female (F) than in control male (M) myocytes. Isoproterenol (ISO, 500 nM) shortened APD90 comparably in M and F, and was largely reversed by beta1-AR blocker CGP 20712A (CGP, 300 nM). Inhibition of IKs with chromanol 293B (10 muM) resulted in less APD prolongation in F at baseline (3.0 vs 8.9 %, p 0.05 vs M) and even in the presence of ISO (5.4 vs 20.9 %, p 0.05). This suggests that much of the ISO-induced APD abbreviation in F is independent of IKs. In F, baseline IKs was 42 % less and was more weakly activated by ISO (19 vs 68 % in M, p 0.01). ISO enhancement of IKs was comparably attenuated by CGP in M and F. After ovariectomy, IKs in F had greater enhancement by ISO (72 %), now comparable to control M. After orchiectomy, IKs in M was only slightly enhanced by ISO (23 %), comparable to control F. Pretreatment with thapsigargin (to block SR Ca release) had bigger impact on ISO-induced APD shortening in F than that in M (p 0.01). In conclusion, we found that there are sex differences in IKs, AP, and their regulation by beta-AR's that are modulated by sex hormones, suggesting the potential for sex-specific antiarrhythmic therapy.
Journal Title: Pflugers Archiv : European journal of physiology
Volume: 465
Issue: 6
ISSN: 1432-2013; 0031-6768
Publisher: Unknown  
Journal Place: Germany
Date Published: 2013
Start Page: 805
End Page: 818
Language: eng
DOI/URL:

10.1007/s00424-012-1193-9
Notes: LR: 20141104; GR: 5UL1 RR025777-03/RR/NCRR NIH HHS/United States; GR: P01 HL080101/HL/NHLBI NIH HHS/United States; GR: R01 HL073966/HL/NHLBI NIH HHS/United States; GR: R01HL046929/HL/NHLBI NIH HHS/United States; GR: R01HL073966/HL/NHLBI NIH HHS/United States; JID: 0154720; 0 (Adrenergic beta-Agonists); 0 (Adrenergic beta-Antagonists); 0 (Delayed Rectifier Potassium Channels); 0 (Gonadal Steroid Hormones); 0 (Potassium Channel Blockers); 0 (Receptors, Adrenergic, beta); RWP5GA015D (Potassium); NIHMS429716; OID: NLM: NIHMS429716; OID: NLM: PMC3634873; 2012/08/27 [received]; 2012/11/28 [accepted]; 2012/11/27 [revised]; 2012/12/15 [aheadofprint]; ppublish