Heterogeneous upregulation of apamin-sensitive potassium currents in failing human ventricles.

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

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

We previously reported that IKAS 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(+) (SK2) channel and apamin-sensitive K(+) currents (IKAS) are upregulated in failing human ventricles. 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). IKAS and action potential were recorded with patch-clamp techniques, and SK2 protein expression was studied by Western blotting. When measured at 1 μmol/L Ca(2+) concentration, IKAS 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). IKAS was lower in the midmyocardial cells than in the epicardial and the endocardial cells. The Ca(2+) dependency of IKAS in HF myocytes was shifted leftward compared to non-HF myocytes (Kd 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). SK2 protein expression was 3-fold higher in HF than in non-HF. There is heterogeneous upregulation of IKAS densities in failing human ventricles. The midmyocardial layer shows lower IKAS densities than epicardial and endocardial layers of cells. Increase in both Ca(2+) sensitivity and SK2 protein expression contributes to the IKAS upregulation.

Original languageEnglish (US)
JournalJournal of the American Heart Association
Volume2
Issue number1
DOIs
StatePublished - Feb 2013
Externally publishedYes

Fingerprint

Apamin
Potassium
Up-Regulation
Heart Failure
Muscle Cells
Action Potentials
Proteins
Aortic Valve Stenosis
Patch-Clamp Techniques
Western Blotting
Rabbits
Biopsy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Heterogeneous upregulation of apamin-sensitive potassium currents in failing human ventricles. / Chang, Po Cheng; Turker, Isik; Lopshire, John C.; Masroor, Saqib; Nguyen, Bich Lien; Tao, Wen; Rubart, Michael; Chen, Peng Sheng; Chen, Zhenhui; Ai, Tomohiko.

In: Unknown Journal, Vol. 2, No. 1, 02.2013, p. e004713.

Research output: Contribution to journalArticle

Chang, Po Cheng ; Turker, Isik ; Lopshire, John C. ; Masroor, Saqib ; Nguyen, Bich Lien ; Tao, Wen ; Rubart, Michael ; Chen, Peng Sheng ; Chen, Zhenhui ; Ai, Tomohiko. / Heterogeneous upregulation of apamin-sensitive potassium currents in failing human ventricles. In: Unknown Journal. 2013 ; Vol. 2, No. 1. pp. e004713.
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AU - Turker, Isik

AU - Lopshire, John C.

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AU - Nguyen, Bich Lien

AU - Tao, Wen

AU - Rubart, Michael

AU - Chen, Peng Sheng

AU - Chen, Zhenhui

AU - Ai, Tomohiko

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