We study ligand-gated ion channels that mediate neuron-neuron and nerve-muscle transmission. Transmitter molecules coax these receptors to change from a closed- to an open-channel conformation. A major goal of our lab is to understand the molecular details of this 'gating' reaction, as well as the other reactions that drive the synaptic response, for example transmitter binding and desensitization. We measure single-channel kinetics to probe the energy landscapes of these reactions (using wild-type and mutant receptors), and relate these results regarding reaction mechanism to the physiological response of the synapse.

Here are some specific topics that are currently being investigated in the lab:

Acetylcholine receptors (neuromuscular transmission):

• Mapping the conformational events that constitute gating (using LFER analysis)
• Measuring 'pre-exponential' factors for gating
• The agonist-dependence of gating, from water to ACh
• The ligand-binding reaction, from water to ACh
• Choline as a contributing factor to slow channel congenital myasthenia
• Mechanisms of desensitization
  

GABA receptors (inhibitory neurotransmission):

• Mapping the conformational events that constitute gating (using LFER analysis)
• The mechanism of action of propofol and other anesthetics
  

NMDA receptors (the slow component of excitatory neurotransmission):

• Understanding the molecular basis of the NMDA-mediated synaptic response
• Modal gating kinetics of NMDA receptors
  

Our group is composed of 10-15 people. Our backgrounds and interests range from neuroscience to physical chemistry, from physiology to biophysics, from biology to chemistry. We all, however, love ion channels, single-molecule measurements, and quantitative thinking.

See the "links" page for a videocast of an April, 2003 seminar, or a quick demo of our ion channel analysis software.