Theory

      The pictures to the right display a cross sectional and bottom view of an KCSA potasium protein channel. The yellow dots are potassium ions (not to scale). The bottom mouth of the pore (see figure 1) would led to the cytoplasmic (inside) region of a cell, and the top opening to the extracellular environment. The channel is defined by four identical transmembrane subunits which are imbedded in a lipid bilayer as "pillars" which form a pore through the membrane (see figure 2).

      This pore permits conductance of potassium across the cell, generally from inside the cell to outside. The transmembrane diffusion of the K+ ions serves to repolarize the cell following the admittance of sodium ion (Na+) current through a corresponding sodium channel.

      This depolarization (sodium in) and subsequent repolarization (potassium out) yields the propagation of nerve signals down a chain of similiar channels (linearly adjacent) firing in the manner of dominoes falling. This casacading polarization transmits the information to the end of the chain. The rate of this propagation is an astounding 20 m/s!

      The figures to the right depict a potassium channel. As alluded to above, sodium has its own channel. Both kinds of channels are highly selective, with diffusion ratios on the order of 10 3 selected ion passes for every one different species passed. How do they do this? K+ is bigger than Na+, so one can see that a sieve effect would be sufficient for the sodium channel. But how about for IRK1 or KCSA? How do they readily pass K+ yet block the smaller Na+?

Figure 1: Cross Section of IRK1

Figure 2: Bottom View of IRK1
Approaches

      The approach essentially consists of using molecular models of these channels as the subject for computer simulations to determine the conductance of ions passing through the channels.

      In terms of models, the recent breakthrough in x-ray diffraction of protein channels by McKinnon et al. has infused a great deal of excitement into the field. This diffraction data represents the first hard evidence which either directly yields the channel configuration (such as with KCSA, the channel McKinnon worked on) or provides a solid template upon which models can be founded (such is the case with IRK1). We use models developed by R. Guy of NIH (Maryland), based on McKinnon's and other data, as the basis of our dynamical simulations.

Figure 3: KCSA P-Loop
Applications

      The applications of Ion Channel work lie primarily within the medical field. For example, the IRK1 channel plays a pertinent role in cardiac functioning. Hence, it is of immediate consequence to understand the basis of channel functioning as this suggests new medical applications, eg. drug design to fix malfunctioning channels.


      With both the new influx of corroborating evidence and the vital applications, the field of ion channels is assured a rewarding and exciting future.

Figure 4: Dipole Model