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Overexpression of the inward rectifier K+ current (I K1 ) accelerates and stabilizes rotors
Author(s) -
Noujaim Sami F.,
Pandit Sandeep,
Vikstrom Karen,
Berenfeld Omer,
Cerrone Marina,
Mironov Sergey,
Lopatin Anatoli,
Jalife Jose
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1157-d
Subject(s) - optical mapping , ventricular fibrillation , conductance , ventricular tachycardia , chemistry , inward rectifier potassium ion channel , electrophysiology , fibrillation , biophysics , medicine , ion channel , biology , atrial fibrillation , physics , biochemistry , receptor , condensed matter physics
It was proposed that I K1 could be important for rotors that cause ventricular tachycardia(VT) and fibrillation(VF). To test this hypothesis, we used a transgenic(TG) mouse line with cardiac‐specific overexpression of Kir2.1‐GFP fusion protein. Optical mapping of ventricular epicardial surface showed that in TG hearts, VT/VF persisted for 350±1181 secs at a very high mean dominant frequency (DF) of 44±4 Hz. In contrast, VT/VF in wild‐type (WT) hearts were short‐lived (3±9 s), and the DF was 26±5 Hz. The stable, fast rotors in TG slowed down, and were terminated by 10 μM Ba 2+ ‐a blocker of I K1 . By increasing I K1 density in a two dimensional computer model with mouse ionic/action potential properties, a stable, fast rotor (45 Hz) could be induced. Simulations suggested that TG hearts allowed fast, stable rotors due to increased excitability because of faster recovery of the Na + current. Simulations also showed that the space constant in TG was smaller than in WT(λ=0.43mm vs. λ=0.66mm). This caused a reduction of rotor core diameter ( CD ). In simulations, mean CD was 3.9±0.3mm in WT and 1.9±0.1mm in TG. In experiments, mean CD was 1.06±0.16mm in WT and 0.6±0.15mm in TG. Finally, simulations showed that rotor DF was more sensitive to upregulating I K1 , compared to other K + currents. These results are the first molecular evidence that I K1 upregulation in the heart is a substrate for stable and very fast rotors. RO1HL060843 to J.J