Heterogeneous Upregulation of Apamin‐Sensitive Potassium Currents in Failing Human Ventricles Article (Web of Science)

abstract

  • Background We previously reported that I KAS are heterogeneously upregulated in failing rabbit ventricles and play an important role in arrhythmogenesis. This study goal is to test the hypothesis that subtype 2 of the small‐conductance Ca 2+ activated K + ( SK 2) channel and apamin‐sensitive K + currents ( I KAS ) are upregulated in failing human ventricles. Methods and Results We studied 12 native hearts from transplant recipients (heart failure [ HF ] group) and 11 ventricular core biopsies from patients with aortic stenosis and normal systolic function (non‐ HF group). I KAS and action potential were recorded with patch‐clamp techniques, and SK 2 protein expression was studied by W estern blotting. When measured at 1 μmol/L Ca 2+ concentration, I KAS was 4.22 (median) (25th and 75th percentiles, 2.86 and 6.96) pA/pF for the HF group (n=11) and 0.98 (0.54 and 1.72) pA/pF for the non‐ HF group (n=8, P =0.008). I KAS was lower in the midmyocardial cells than in the epicardial and the endocardial cells. The Ca 2+ dependency of I KAS in HF myocytes was shifted leftward compared to non‐ HF myocytes ( K d 314 versus 605 nmol/L). Apamin (100 nmol/L) increased the action potential durations by 1.77% (−0.9% and 7.3%) in non‐ HF myocytes and by 11.8% (5.7% and 13.9%) in HF myocytes ( P =0.02). SK 2 protein expression was 3‐fold higher in HF than in non‐ HF . Conclusions There is heterogeneous upregulation of I KAS densities in failing human ventricles. The midmyocardial layer shows lower I KAS densities than epicardial and endocardial layers of cells. Increase in both Ca 2+ sensitivity and SK 2 protein expression contributes to the I KAS upregulation.

authors

  • Chang, Po‐Cheng
  • Turker, Isik
  • Lopshire, John C.
  • Nguyen, Bich‐Lien
  • Tao, Wen
  • Rubart, Michael
  • Chen, Peng‐Sheng
  • Chen, Zhenhui
  • Ai, Tomohiko

publication date

  • 2013

webpage

published in

volume

  • 2

issue

  • 1