Yellen Lab Research Interests

The Moving Parts of Voltage-gated Ion Channels

All electrical signaling in the nervous system is controlled by ion channels, a class of membrane proteins that form pores through the membrane. Charged ions such as sodium, potassium and calcium pass through ion channels and carry an electrical current. The channels themselves are regulated, so that the pores are only open when the proper chemical or electrical signal is present, and only certain ions can pass through a particular kind of channel. By understanding how channels open and close and how they are regulated, we define the repertoire of molecular changes used by neurons when they signal, sense, and learn.

We use single channel biophysics and directed mutagenesis to relate ion channel function to structure. Often we introduce individual cysteine residues into the channel protein; these cysteines serve as targets for chemical modification and for metal binding. For instance, when introduced at just the right place in the moving parts of the channel protein, a pair of cysteines can be bridged by a metal ion (such as Cd2+). If the metal bridges are compatible with only some of the functional conformations of the channel, they influence gating: for instance, they can lock the channel in an open state or in a closed state.

We have applied this approach, together with looking at the state-dependent rate of chemical modification of cysteines, to learn about the moving parts of both voltage-gated K+ channels and voltage-gated pacemaker (HCN) channels.


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