Referenced in: none

Automatically associated channels: Kir2.1 , Kir2.3

Title: Blockade of the inward rectifying potassium current terminates ventricular fibrillation in the guinea pig heart.

Authors: Mark Warren, Prabal K Guha, Omer Berenfeld, Alexey Zaitsev, Justus M B Anumonwo, Amit S Dhamoon, Suveer Bagwe, Steven M Taffet, José Jalife

Journal, date & volume: J. Cardiovasc. Electrophysiol., 2003 Jun , 14, 621-31

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12875424

Abstract
Stable high-frequency rotors sustain ventricular fibrillation (VF) in the guinea pig heart. We surmised that rotor stabilization in the left ventricle (LV) and fibrillatory conduction toward the right ventricle (RV) result from chamber-specific differences in functional expression of inward rectifier (Kir2.x) channels and unequal IK1 rectification in LV and RV myocytes. Accordingly, selective blockade of IK1 during VF should terminate VF.Relative mRNA levels of Kir2.x channels were measured in LV and RV. In addition, LV (n = 21) and RV (n = 20) myocytes were superfused with BaCl2 (5-50 micromol/L) to study the effects on IK1. Potentiometric dye-fluorescence movies of VF were obtained in the presence of Ba2+ (0-50 micromol/L) in 23 Langendorff-perfused hearts. Dominant frequencies (DFs) were determined by spectral analysis, and singularity points were counted in phase maps to assess VF organization. mRNA levels for Kir2.1 and Kir2.3 were significantly larger in LV than RV. Concurrently, outward IK1 was significantly larger in LV than RV myocytes. Ba2+ decreased IK1 in a dose-dependent manner (LV change > RV change). In baseline control VF, the fastest DF domain (28-40 Hz) was located on the anterior LV wall and a sharp LV-to-RV frequency gradient of 21.2 +/- 4.3 Hz was present. Ba2+ significantly decreased both LV frequency and gradient, and it terminated VF in a dose-dependent manner. At 50 micromol/L, Ba2+ decreased the average number of wavebreaks (1.7 +/- 0.9 to 0.8 +/- 0.6 SP/sec x pixel, P < 0.05) and then terminated VF.The results strongly support the hypothesis that IK1 plays an important role in rotor stabilization and VF dynamics.