Proinflammatory Cytokine Modulates Intracellular Calcium Handling and Enhances Ventricular Arrhythmia Susceptibility.

The mechanism of Interleukin-17 (IL-17) induced ventricular arrhythmia (VA) remains unclear. This study aimed to investigate the effect of intracellular calcium (Ca) handling and VA susceptibility by IL-17. The electrophysiological properties of isolated perfused rabbit hearts under IL-17 (20 ng/ml, = 6) and the IL-17 with neutralizer (0.4 μg/ml, = 6) were evaluated using an optical mapping system. The action potential duration (APD) and Ca transient duration (CaTD) were examined, and semiquantitative reverse transcriptase-polymerase chain reaction analysis of ion channels was performed. There were longer APD, CaTD and increased thresholds of APD and CaTD alternans, the maximum slope of APD restitution and induction of VA threshold in IL-17 group compared with those in IL-17 neutralizer and baseline groups. During ventricular fibrillation, the number of phase singularities and dominant frequency were both significantly greater in IL-17 group than in baseline group. The mRNA expressions of the Na/Ca exchanger, phospholamban, and ryanodine receptor Ca release channel were upregulated, and the subunit of L-type Ca current and sarcoplasmic reticulum Ca-ATPase 2a were significantly reduced in IL-17 group compared to baseline and IL-17 neutralizer group. IL-17 enhanced CaTD and APD alternans through disturbances in calcium handling, which may increase VA susceptibility.