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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 I Ks 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 I Ks 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.

Original languageEnglish (US)
Pages (from-to)805-818
Number of pages14
JournalPflugers Archiv European Journal of Physiology
Volume465
Issue number6
DOIs
StatePublished - Jun 2013

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pamidronate
Sex Characteristics
Action Potentials
Potassium
Rabbits
Thapsigargin
Orchiectomy
Clamping devices
Gonadal Steroid Hormones
Ovariectomy
Isoproterenol
Adrenergic Receptors
Muscle Cells

Keywords

  • Adrenergic receptor
  • Potassium current
  • Repolarization
  • Sex differences

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic stimulation in rabbits. / Zhu, Yujie; Ai, Xun; Oster, Robert A.; Bers, Donald M; Pogwizd, Steven M.

In: Pflugers Archiv European Journal of Physiology, Vol. 465, No. 6, 06.2013, p. 805-818.

Research output: Contribution to journalArticle

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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 I Ks 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 I Ks 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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