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

  • Ion Channels, Receptors and Transporters
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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 β-adrenergic receptors (β-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 β1-AR blocker CGP 20712A (CGP, 300 nM). Inhibition of IKs with chromanol 293B (10 μM) 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 β-AR’s that are modulated by sex hormones, suggesting the potential for sex-specific antiarrhythmic therapy.

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Acknowledgements

This study was supported by National Heart, Lung, and Blood Institute Grants R01HL073966 and R01HL046929 (to SMP) and partially supported by 5UL1 RR025777-03 from the NIH National Center for Research Resources.

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  1. Department of Medicine, University of Alabama at Birmingham, 1670 University Blvd, Birmingham, AL, 35294, USA

    Yujie Zhu, Xun Ai, Robert A. Oster & Steven M. Pogwizd

  2. Department of Pharmacology, University of California, Davis, Davis, CA, 95616, USA

    Donald M. Bers

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  1. Yujie Zhu
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Zhu, Y., Ai, X., Oster, R.A. et al. Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic stimulation in rabbits. Pflugers Arch - Eur J Physiol 465, 805–818 (2013). https://doi.org/10.1007/s00424-012-1193-9

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