, 2012 and Hille, 2001). Ion channel proteins form holes in membranes that open and close in response to various chemical and electrical stimuli. These structures allow cells to tap into the energy stored selleck chemicals llc in transmembrane ionic gradients to generate the electrical signals that race through our nerves and muscles. In 1988, when Neuron launched, it published 21 papers devoted to some aspect of ion channel research in its first year. These covered topics spanning from basic channel biophysics to the behavior of channels in complex systems. In reflecting on the questions that motivated ion channel research 25 years ago, it is striking that the

spirit, if not the details, of the studies exemplified

in Neuron’s inaugural year mark many of the same questions that occupy the field today. These include: what is the physical nature of a channel ( Auld et al., 1988, Ballivet et al., 1988, Deneris et al., 1988, Levitan et al., 1988, Lotan et al., 1988, Rudy et al., 1988 and Timpe http://www.selleckchem.com/GSK-3.html et al., 1988)? How do ions and pharmacological tools interact with channel pores ( MacKinnon et al., 1988, Miller, 1988 and Miller et al., 1988)? Where are particular channels expressed ( Harris et al., 1988, Siegel, 1988, Wang et al., 1988, Wisden et al., 1988 and Wollner et al., 1988) and how is this regulated by development or electrical activity ( Goldman et al., 1988 and Hendry and Jones, 1988)? much How do channels respond to manipulations in diverse types of excitable cells ( Doerner and Alger, 1988, Haydon and Man-Son-Hing, 1988, Lechleiter et al., 1988, Lipscombe et al., 1988, Maricq and Korenbrot, 1988, Pfaffinger et al., 1988 and Yakel and Jackson, 1988)? At the silver anniversary of the journal, we reflect on how much the field has changed, how certain classes of questions persist, and highlight some key open questions that rest upon the major achievements

of the past quarter century but that still represent areas of great opportunity for discovery. The ion channel field is vast and it would take a book to do it justice. Great progress has been made in understanding how channels “gate” their pores. To capture some of this excitement in a short space, we focus on three areas of phenomenal advancement that frame key unaddressed problems: (1) the transformation from cartoon to three dimensions of our understanding of the molecular nature of channels, (2) a tale of one mechanism that is central to understanding neural signaling, voltage sensing, and (3) how the complicated, multicomponent protein complexes of channels are assembled and delivered to the right place in the cell. These basic issues permeate the biological functions of all ion channels and understanding such facets of channel biology remains critical for unraveling how channels operate in normal and disease states.