The functional impact of a channel is shaped not only by its kinetic properties, but also by its location in the membrane. We have methods to map the spatial distribution of ion channels or to measure their biophysical properties — two approaches that have followed separate paths. But as Korchev et al . report in Nature Cell Biology, the combination of patch-clamp and scanning probe microscopy (SPM) is starting to bridge this divide.

In SPM, a pipette is placed within a few nanometres of the cell and moved over the specimen. Current through the pipette depends on the distance between the tip and the membrane. Whenever the pipette moves closer to the cell during the scan, the change in current acts as a signal to restore their original separation. By plotting the three-dimensional displacement of the pipette, a detailed topographic map of the cell surface is obtained.

Korchev et al. combined SPM with patch-clamp recordings to detect ATP-regulated K+channels in cardiac myocytes. Their SPM pipette contained a high K+ concentration such that the passage of the tip over an open channel during the scan led to current flow through the membrane, which was recorded by a second pipette — the patch-clamp electrode. By scanning a cell repetitively, they could generate maps that, besides the topographic data, contained information about the position of the channels and how often they were open.

The joint application of SPM and patch-clamp to the study of neurons is a promising development. For example, using this combination of techniques on dendrites should provide insights into the workings of their active conductances, which continue to be largely terra incognita.