204 GROUP I AND II METALS IN BIOLOGICAL SYSTEMS
visualize ions fl owing through channels that can be opened and closed by dif-
ferent cellular signals. In 1998, the MacKinnon group published the fi rst struc-
tural study of a potassium ion channel, a feat welcomed by the scientifi c
community eager to learn the physical details of ion channel workings (PDB:
1BL8).^15 Since then, a variety of potassium and other ion channel structures
have been published, leading to a greater understanding of these important
systems. The potassium ion channel structural studies will be detailed in the
following sections. Following their initial success, the MacKinnon group pub-
lished the structure of the cytoplasmic β subunit - T1 complex of voltage -
dependent K + ion channels in 2000 showing the connection between the
ion channel pore and these larger structures within the cytoplasm. The article
also explained how inactivation peptides reach their action site through lateral,
negatively charged openings between the cytoplasmic β subunit - T1 complex
and the ion channel pore (PDB: 1EXB).^16 In 2001, MacKinnon ’ s group pub-
lished the structure of a potassium ion channel – monoclonal antibody (Fab)
complex that further explained how ions to be transported have their hydra-
tion shells removed or reattached and how the ion channel selectivity fi lter
changes its coordination pattern in response to high or low K + ion concentra-
tion (PDB: 1K4C, 1K4D).^17 The MacKinnon group next turned its attention
to voltage - dependent K + ion channels that open to allow ion passage in
response to changes in cell membrane voltage. The research identifi ed “ voltage -
sensor paddles ” that move in response to membrane voltage changes and that
carry positive charge across membranes (PDB: 1ORS, 1ORQ).^18 More recently,
in 2005, MacKinnon and co - workers have published details of Shaker family
voltage - dependent K + (K v ) ion channels to show how voltage sensors operate
to open and close the ion pore and how the complex ’ s β subunits help regulate
the channels (PDB: 2A79).^19 Also in 2005, the MacKinnon group presented
two structures of the voltage - dependent channel KvAP with and without
monoclonal antibody fragments (PDB: 2A0L).^20 In 2006, the group published
fi ndings on ion selectivity in a semisynthetic K + channel locked into a conduc-
tive conformation (PDB: 2IH1 and 2IH3).^21
Physically, ion channels are tiny pores that stud the surface of all cells. The
ion channels are important for, among other things, the function of muscles
and the nervous system. These channels allow the passage of potassium,
calcium, sodium, and chloride ions. Through a balance of electrical forces and
chemical bonds, ion channels are specifi c for one ion; for instance, a potassium
ion channel will reject a sodium ion trying to enter its channel. An excellent
visualization of the overall process is found at the website http://www.
rockefeller.edu/pubinfo/howkion.html. It will be helpful to look at this
website before going any further in the discussion.
Potassium channels are part of a complex system that helps maintain the
normal ionic balance across the cell membrane. In excitable cells, like those
in nerves and muscles, the channels also help reestablish the electrical differ-
ence between the inside and outside of the cells after excitation. In the case
of neuron fi ring, potassium ions, and thus positive charge, builds up inside the