Document resource
According to the world health organisation 99% of the global population are exposed to poor air quality. This is often linked with poor cardiovascular health, which can manifest as cardiac arrhythmia. Though it isn’t clear the primary pathological mechanisms underlying pollutant-gas induced arrhythmias. This study aims to identify pollutant gas, carbon monoxide (CO), sensitive cardiac ion channels and identify its direct effect on cardiac cell function.Carbon monoxide releasing molecule (CORM-2, Sigma Aldrich, 288144) was utilised throughout. Voltage-gated cardiac ion channel (hERG, Nav1.5, and Cav3.2) activity was measured in overexpressing HEK or CHO cell lines using automated whole-cell voltage-patch clamp (Q-patch, Sophion), and hIPSC-ventricular cardiomyocyte (Axol, AX2508) function was monitored using multielectrode array (Maestro-edge, Axion).IC50 values revealed CORM-2 significantly inhibited delayed fast rectifier potassium channel, IhERG (28 µM, n = 4, p < 0.0001), T-type calcium channel,ICav3.2 (42 µM, n = 4, p < 0.0001), and sodium ion channel, INav1.5 (peak 1 = 52 µM, peak 8 = 59 µM, n = 6, p < 0.0001) relative to inactive (i)CORM-2.Relative to iCORM-2, 100 µM CORM decreased beat amplitude and beat period at 120-minutes post dose (n = 4), and significantly decreased action potential duration (APD) at 30, 60- and 120-minutes post dose (p < 0.001).Our preliminary findings suggest that CO may contribute to arrhythmic traits through targeting voltage gated cardiac ion channels but also intracellular ion channels. Future work will increase study power and elucidate the underlying mechanisms, to determine if these are direct or indirect effects of CO.