Structure that Opens the Gate and Opens the Door

Sometimes the best way to solve a problem is to look at it from a different perspective. That is certainly the case in ion channel research. Hodgkin and Huxley must have realized that 50 years ago when they looked at membrane currents with a voltage clamp, and Sakmann and Neher realized it 20 years ago when they measured Possible Symmetries of Tetrameric Channel single-channel currents with the patch-clamp technique. The cloning and mutagenesis of ion channel The BK channel is particularly interesting because it is cDNAs over the past decade has also provided a new gated by both voltage and intracellular Ca 2ϩ. The voltage perspective into the molecular mechanisms of ion chan-gating is presumed to result from movement of the S4 nel function. Most recently, however, it has been struc-segments, while the Ca 2ϩ appears to bind to an intracel-tural determination of ion channels that has been provid-lular domain in the carboxy-terminal region referred to ing the new perspectives. In this issue of Neuron, as the Ca 2ϩ bowl (Schreiber and Salkoff, 1997). Both the MacKinnon and his colleagues provide another look at movement of the S4 segments and the binding of Ca 2ϩ to the structure of a K ϩ channel, this time an intracellular each subunit are thought to modulate the same opening domain of the E. coli K ϩ channel, which is also present conformational change in the pore (Horrigan et al., 1999; in large conductance Ca 2ϩ-activated K ϩ channels (BK Rothberg and Magleby, 1999). This highlights the con-channels) (Jiang et al., 2001). This domain, following the servation in the mechanisms of voltage-dependent gat-inner helix of the pore, is in a region of the channel ing and ligand-dependent gating. One domain, between thought to couple intracellular ligand binding to the con-the inner helix and the Ca 2ϩ bowl, is particularly intri-formational change that opens the channel pore. This guing given its location and strong conservation. This structure promises to yield new insights into the molecu-domain, now referred to as the RCK (for regulating con-lar mechanisms of gating. ductance of potassium) domain, is found not only in Channels that are gated by intracellular ligands are BK channels, but also in a majority of prokaryotic K ϩ beginning to take their rightful place beside the voltage-channels and in TrkA, an intracellular component of the gated and neurotransmitter-gated channels. These Trk system of prokaryotic K ϩ transporters. In …