Summary
We propose that the following principles
underlie the structure and operation of K1
channels. (i) The pore is constructed of an
inverted teepee, with the selectivity filter
held at its wide end. This architecture also
describes the pore of cyclic nucleotide–
gated channels and probably Na1 and
Ca21 channels as well. (ii) The narrow
selectivity filter is only 12 Å long, whereas
the remainder of the pore is wider and has
a relatively inert hydrophobic lining.
These structural and chemical properties
favor a high K1 throughput by minimizing
the distance over which K1 interacts
strongly with the channel. (iii) A large
water-filled cavity and helix dipoles help
to overcome the high electrostatic energy
barrier facing a cation in the low dielectric
membrane center. (iv) The K1 selectivity
filter is lined by carbonyl oxygen atoms,
which provide multiple closely spaced
sites. The filter is constrained in an opti-