POTASSIUM-DEPENDENT MOLECULES 205
cell. The charged ions create an electrical voltage across the cell membrane.
This buildup in turn causes the potassium channel to open, spilling out potas-
sium ions and restoring the cell to its resting state. The proteins that manage
the neuronal system are called potassium voltage - gated ion channels. The so -
called “ action potential ” of nerve cells is generated when an ion channel on
the surface of a nerve cell is opened by a chemical signal sent from an adjacent
nerve cell, whereupon an electrical pulse is propagated along the surface of
the nerve cell through the opening and closing of other ion channels in the
course of a few milliseconds. Rapid - fi re opening and closing of these channels
releases ions, moving electrical impulses from the brain in a wave to their
destination in the body. Without potassium and sodium channels, neurons
could not generate electrical signals and hearts could not beat rhythmically.
In this discussion, we will concentrate on several potassium ion channel pro-
teins whose function it is to generate nerve impulses — the electrical activity
that underlies all movement, sensation, and perhaps even thought. Malfunc-
tioning ion channels contribute to disease states such as diabetes, epilepsy,
arrhythmia (irregular heart beat), and others. The research now being carried
out by the many groups studying ion channel structure and function may play
an important role in the development of drugs to deal with these diseases.
Finding protein sequence information (the primary sequence of amino acids
in a protein chain) is often important to understand researchers ’ explanations
of their experimental work, especially for the large variety of potassium ion
channels being discussed in the next section. An excellent database for fi nding
sequence information is the ExPASy (Expert Protein Analysis System) pro-
teomics server of the Swiss Institute of Bioinformatics (SIB) at http://www.
expasy.org/. At this site, search the protein knowledgebase Swiss - Prot and
TrEMBL.
5.4.2.2 X-Ray Crystallographic Studies. In 1998 when the fi rst X - ray crys-
tallographic structure of a K + channel was published by his group (PDB:
1BL8), MacKinnon and fellow researchers had been studying potassium ion
channels for at least a decade. They had used site - directed mutagenesis to
determine a “ signature sequence ” of eight amino acids that were essential to
the K + channel ’ s function. The mutations were carried out on the so - called
Shaker potassium channel from fruit fl ies whose DNA (and therefore amino
acid) sequence had been determined in 1987.^22 At this time, researchers also
knew that K + channels consisted of four subunits, with each one contributing
its fi ve amino acid signature sequence — TVGYG — to form a selectivity fi lter
for potassium ions to the exclusion of all others. However, to know with cer-
tainty what the chemistry and mechanism of potassium ion selectivity could
be, structural analysis at atomic scale was needed. The potassium ion channel
history is complex and somewhat confusing. It will be helpful if the reader has
a full complement of the fi gures contained in this section and those recom-
mended for viewing from the publications referenced here. Information on the
various potassium ion channel structural studies is collected in Table 5.3. The