A, whole-cell configuration. Application of 50 μg ml−1 LPS decreased mean whole-cell current IhHCN2 at a test potential of −100 mV to about 65% (n = 4 each). B, cell-attached recordings (macro-patch) with LPS applied via the bath solution. The patch electrode protects the channels under investigation from direct interaction with LPS. However, LPS remained able to induce receptor-mediated intracellular signalling, thereby modulating channel activity. Representative IhHCN2 traces were recorded in the absence of LPS (control) and after application of 50 μg ml−1 LPS. Mean current amplitude of IhHCN2 did not differ between control and LPS treatments (n = 8 each). C, cell-attached recordings with LPS applied via the pipette solution. Action of LPS is spatially restricted to the vicinity of the channels under investigation. This experimental configuration does not allow for paired experiments. Therefore, activation curves were recorded with or without 50 μg ml−1 LPS included in the pipette solution (n = 3 each). Potential of half-maximal activation (V0.5) is shifted by LPS to more negative potentials. *P < 0.05 versus control.