Richard Horn, PhD

Contact Dr. Horn

900 Walnut St.

Philadelphia, PA 19107

(215) 503-6725
(215) 503-2073 fax

What Molecular Properties Underline Ion Channel Function?

My research focuses on the voltage-dependent sodium and potassium channels that underlie action potentials in excitable cells, such as nerve and muscle cells. What makes these ion channels so exquisitely sensitive to membrane potential and so selective for their preferred ions? General answers to these questions are known, but glaring ignorance persists. We seek molecular, and indeed atomic, information on the detailed mechanics of these dynamic proteins, including an accounting of their internal movements and the energetics of their interactions with ions and modulatory molecules.

The techniques that I use in my research include mutations of individual amino acids of the channel protein, heterologous expression and electrophysiological assays. Our lab recently started to use the method of nonsense suppression that permits the generation of unnatural mutations within ion channels expressed in Xenopus oocytes. Although challenging, this technology allows virtually limitless possibilities for side-chain structures.

I hope that my findings will be used to enhance our understanding of the basic properties of ion channels, how they may be altered in disease states, and how diseases of excitability can be controlled.

Publications

Most recent Peer-reviewed Publications

1. Structural biology: Peering into the spark of life
2. Channels get in an HUFA: RNA editing gets them out of a jam
3. An electrostatic interaction between TEA and an introduced pore aromatic drives spring-in-the-door inactivation in Shaker potassium channels
4. Uncooperative voltage sensors
5. Regulated RNA editing and functional epistasis in shaker potassium channels
6. Characterization of five RNA editing sites in Shab potassium channels
7. Electrostatic contributions of aromatic residues in the local anesthetic receptor of voltage-gated sodium channels
8. New insights into the therapeutic inhibition of voltage-gated sodium channels
9. Calcium block of single sodium channels: Role of a pore-lining aromatic residue
10. A cation-π interaction discriminates among sodium channels that are either sensitive or resistant to tetrodotoxin block
11. Physiology: Legacy of leaky channels
12. A cation-π interaction between extracellular TEA and an aromatic residue in potassium channels
13. Electrifying phosphatases.
14. Focused electric field across the voltage sensor of potassium channels
15. Investigating the putative glycine hinge in Shaker potassium channel
16. How ion channels sense membrane potential
17. Modulation of the cardiac sodium channel Nav1.5 by Fyn, a Src family tyrosine kinase
18. Stirring up controversy with a voltage sensor paddle
19. Specificity of Charge-carrying Residues in the Voltage Sensor of Potassium Channels
20. How S4 Segments Move Charge. Let Me Count the Ways

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