Pauli Lectures 2007

Living organisms are electrical. Our brains instruct our muscles to move by transmitting information, which is encoded in the form of electrical impulses that travel along nerve fibers. Our ability to experience our world through vision, smell, taste, hearing and touch depends upon the transmission of electrical signals. Even our ability to think is based upon the complex electrical interactions of neurons in our central nervous system. How does ‘animal electricity’ work? How does it relate to inanimate electrical devices such as electric toasters, televisions and computers? The history of ‘animal electricity’ and how scientists figured it out is very interesting. It is interesting not only because it leads us to an understanding of the subject, but also because it exemplifies the strange and unexpected manner in which scientific ideas evolve. In this lecture I will describe from a historical perspective how studies of ‘animal electricity’ actually advanced the understanding of electricity in physics. I will also explain the basic principles of life’s electrical system by describing ion channels as the conductors of electricity in living cells.

The smallest of living organisms rely solely on molecular diffusion for the transfer of chemical ‘information’. But the time it takes for a molecule to diffuse is proportional to the square of the distance, which means molecular diffusion is a far too slow process for information transfer for all but the tiniest of living organisms. For longer distances, life evolved a rapid system of information transfer in the form of electrical impulses known as action potentials: these propagate along the membrane of cells at many tens of meters per second. Proteins known as voltage-dependent ion channels make action potentials possible. This lecture will focus on the voltage-dependent potassium ion channel. Together with the ability to conduct potassium ions across the cell membrane these ion channels exhibit their namesake property of ‘voltage-dependence’, which means that they are equipped with a molecular voltmeter that enables them to sense the cell membrane voltage and open or close accordingly. Voltage-dependent ion channels are nature’s analog of the field effect transistor. The atomic structure of the voltage-dependent potassium channel will be presented and its mechanism discussed.

Ion channels, like enzymes, have their specific substrates: potassium, sodium, calcium, and chloride channels permit only their namesake ions to diffuse through their pores. Potassium channels exhibit a remarkable ability to discriminate between potassium and sodium—by a factor of nearly 10,000—even though these ions are similar in size (1.33 and 0.95 Å, respectively). Such exquisite selectivity is impressive when one considers that potassium flows though the pore at a rate approaching the diffusion limit. My laboratory has determined the atomic structures of several potassium channels. The architecture of the pore allows potassium ions to remain hydrated at the center of the membrane, where the dielectric barrier to ion flow is expected to be greatest. The selectivity filter coordinates dehydrated potassium ions, but not sodium ions, thus accounting for ion selectivity. Structural and thermodynamic data on the binding of various ions to the selectivity filter will be discussed. A detailed conduction mechanism in which two potassium ions adopt two configurations within four binding sites is hypothesized to account for near diffusion-limited conduction rates.