Fitting Kv potassium channels in the PIP2 puzzle

Potassium channels, microscopic pores that allow potassium ions to cross cell membranes, are crucial to such diverse processes as conduction of the nerve impulse, regulation of the heartbeat, and the secretion of hormones such as insulin. PIP₂, a minor phospholipid component of cell membranes, regulates the activity of various proteins in the cell membrane, and previous studies have indicated that it might be a very important regulator of such channels.

To probe the cell signaling roles of PIP₂ under physiological conditions, Bertil Hille (University of Washington) and colleagues used a set of sophisticated molecular tools to rapidly deplete PIP₂ in the membranes of intact cells and simultaneously monitor the PIP₂ changes that occurred.

Using this approach, they confirmed previous studies showing that the activity of "inward rectifier" potassium channels was strongly dependent on PIP₂. Surprisingly, however, they found that various members of the Kv channel family thought to be PIP₂ sensitive on the basis of studies that analyzed their activity in isolated patches of cell membrane were, in fact, unaffected by PIP₂ depletion. Thus, the group demonstrated that large PIP₂ changes at the membranes of intact cells did not modulate the function of these Kv channels, contrary to expectations.

According to Donald Hilgemann (UT Southwestern Medical Center at Dallas) in commentary appearing in the September 2012 issue of JGP, the findings are an important step forward in our understanding of PIP₂ effects on Kv channels. Furthermore, the tools employed by the Hille group can now be used to address questions about PIP₂ functions in other cellular processes. In addition to its complex roles in cytoskeleton regulation and endocytosis, PIP₂ appears to influence many cell membrane processes, including the formation of membrane domains, membrane budding, and membrane turnover.