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Apamin-sensitive calcium-activated potassium currents in rabbit ventricles with chronic myocardial infarction.

AbstractINTRODUCTION:
The apamin-sensitive small-conductance calcium-activated potassium current (IKAS ) is increased in heart failure. It is unknown if myocardial infarction (MI) is also associated with an increase of IKAS .
METHODS AND RESULTS:
We performed Langendorff perfusion and optical mapping in 6 normal hearts and 10 hearts with chronic (5 weeks) MI. An additional 6 normal and 10 MI hearts were used for patch clamp studies. The infarct size was 25% (95% confidence interval, 20-31) and the left ventricular ejection fraction was 50 (46-54). The rabbits did not have symptoms of heart failure. The action potential duration measured to 80% repolarization (APD80 ) in the peri-infarct zone (PZ) was 150 (142-159) milliseconds, significantly (P = 0.01) shorter than that in the normal ventricles (167 [158-177] milliseconds. The intracellular Ca transient duration was also shorter in the PZ (148 [139-157] milliseconds) than that in normal ventricles (168 [157-180] milliseconds; P = 0.017). Apamin prolonged the APD80 in PZ by 9.8 (5.5-14.1)%, which is greater than that in normal ventricles (2.8 [1.3-4.3]%, P = 0.006). Significant shortening of APD80 was observed at the cessation of rapid pacing in MI but not in normal ventricles. Apamin prevented postpacing APD80 shortening. Patch clamp studies showed that IKAS was significantly higher in the PZ cells (2.51 [1.55-3.47] pA/pF, N = 17) than in the normal cells (1.08 [0.36-1.80] pA/pF, N = 15, P = 0.019).
CONCLUSION:
We conclude that IKAS is increased in MI ventricles and contributes significantly to ventricular repolarization especially during tachycardia.
AuthorsYoung Soo Lee, Po-Cheng Chang, Chia-Hsiang Hsueh, Mitsunori Maruyama, Hyung Wook Park, Kyoung-Suk Rhee, Yu-Cheng Hsieh, Changyu Shen, James N Weiss, Zhenhui Chen, Shien-Fong Lin, Peng-Sheng Chen
JournalJournal of cardiovascular electrophysiology (J Cardiovasc Electrophysiol) Vol. 24 Issue 10 Pg. 1144-53 (Oct 2013) ISSN: 1540-8167 [Electronic] United States
PMID23718850 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2013 Wiley Periodicals, Inc.
Chemical References
  • Potassium Channel Blockers
  • Potassium Channels, Calcium-Activated
  • Apamin
  • Potassium
Topics
  • Action Potentials
  • Animals
  • Apamin (pharmacology)
  • Cardiac Pacing, Artificial
  • Chronic Disease
  • Disease Models, Animal
  • Electrocardiography
  • Female
  • Heart Rate
  • In Vitro Techniques
  • Kinetics
  • Myocardial Infarction (metabolism, pathology, physiopathology)
  • Myocardium (metabolism, pathology)
  • Patch-Clamp Techniques
  • Perfusion
  • Potassium (metabolism)
  • Potassium Channel Blockers (pharmacology)
  • Potassium Channels, Calcium-Activated (antagonists & inhibitors, metabolism)
  • Rabbits
  • Stroke Volume
  • Tachycardia (metabolism, physiopathology)
  • Ventricular Function, Left

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