Skip to main content
Download PDF
- Main
Small‐Conductance Calcium‐Activated Potassium Current Is Activated During Hypokalemia and Masks Short‐Term Cardiac Memory Induced by Ventricular Pacing
Published Web Location
https://doi.org/10.1161/circulationaha.114.015125Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
For improved accessibility of PDF content, download the file to your device.
Enter the password to open this PDF file:
File name:
-
File size:
-
Title:
-
Author:
-
Subject:
-
Keywords:
-
Creation Date:
-
Modification Date:
-
Creator:
-
PDF Producer:
-
PDF Version:
-
Page Count:
-
Page Size:
-
Fast Web View:
-
Preparing document for printing…
0%