Small-Conductance Calcium-Activated Potassium Current Is Activated During Hypokalemia and Masks Short-Term Cardiac Memory Induced by Ventricular Pacing.

Abstract

BACKGROUND:

Hypokalemia increases the vulnerability to ventricular fibrillation. We hypothesize that the apamin-sensitive small-conductance calcium-activated potassium current (IKAS) is activated during hypokalemia and that IKAS blockade is proarrhythmic.

METHODS AND RESULTS:

Optical mapping was performed in 23 Langendorff-perfused rabbit ventricles with atrioventricular block and either right or left ventricular pacing during normokalemia or hypokalemia. Apamin prolonged the action potential duration (APD) measured to 80% repolarization (APD80) by 26 milliseconds (95% confidence interval [CI], 14-37) during normokalemia and by 54 milliseconds (95% CI, 40-68) during hypokalemia (P=0.01) at a 1000-millisecond pacing cycle length. In hypokalemic ventricles, apamin increased the maximal slope of APD restitution, the pacing cycle length threshold of APD alternans, the pacing cycle length for wave-break induction, and the area of spatially discordant APD alternans. Apamin significantly facilitated the induction of sustained ventricular fibrillation (from 3 of 9 hearts to 9 of 9 hearts; P=0.009). Short-term cardiac memory was assessed by the slope of APD80 versus activation time. The slope increased from 0.01 (95% CI, -0.09 to 0.12) at baseline to 0.34 (95% CI, 0.23-0.44) after apamin (P<0.001) during right ventricular pacing and from 0.07 (95% CI, -0.05 to 0.20) to 0.54 (95% CI, 0.06-1.03) after apamin infusion (P=0.045) during left ventricular pacing. Patch-clamp studies confirmed increased IKAS in isolated rabbit ventricular myocytes during hypokalemia (P=0.038).

CONCLUSIONS:

Hypokalemia activates IKAS to shorten APD and maintain repolarization reserve at late activation sites during ventricular pacing. IKAS blockade prominently lengthens the APD at late activation sites and facilitates ventricular fibrillation induction.

• Authors: Yi-Hsin Chan, Wei-Chung Tsai, Jum-Suk Ko, Dechun Yin, Po-Cheng Chang, Michael Rubart, James N Weiss, Thomas H Everett 4th, Shien-Fong Lin, Peng-Sheng Chen
• Journal: Circulation (Circulation) Vol. 132 Issue 15 Pg. 1377-86 (Oct 13 2015) ISSN: 1524-4539 [Electronic] United States
• PMID: 26362634 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Intermediate-Conductance Calcium-Activated Potassium Channels
• Potassium Channel Blockers
• Apamin
• Potassium

Topics

• Action Potentials (drug effects)
• Animals
• Apamin (pharmacology)
• Cardiac Pacing, Artificial (adverse effects)
• Disease Susceptibility
• Heart Conduction System (drug effects, physiopathology)
• Heart Ventricles (physiopathology)
• Hypokalemia (complications, physiopathology)
• Intermediate-Conductance Calcium-Activated Potassium Channels (antagonists & inhibitors, physiology)
• Myocytes, Cardiac (drug effects, physiology)
• Patch-Clamp Techniques
• Potassium (physiology)
• Potassium Channel Blockers (pharmacology)
• Rabbits
• Ventricular Fibrillation (etiology, physiopathology, prevention & control)
• Voltage-Sensitive Dye Imaging