Differential reduction of HCN channel activity by various types of lipopolysaccharide

► LPS strongly influences the biophysical properties of cardiac pacemaker channels. ► Pro-inflammatory Lipid A is not essential for impairing channel activity. ► In contrast, the O-chain is a prerequisite for the inhibition of If by LPS. ► The impact of LPS on If may affect HRV contributing to cardiac dysfunction in sepsis.