Molecular mechanisms that underlie gating in voltage-dependent ion channels

The objective of Dr. Chanda’s research is to understand how structure and dynamics determine the function of the voltage-dependent ion channels. In response to a change in membrane potential, voltage-dependent ion channels undergo a series of conformational changes culminating in the opening or closing of the channel.  The Chanda lab uses a variety of biophysical methods to track the structural dynamics of these processes. Electrophysiological methods like ionic and "gating" current measurements provide information about the global structural changes. Site-specific fluorescence recordings and cysteine accessibility methods, on the other hand, provide information about the local structural changes in the protein. These methods complement one another and together they provide a detailed physical model of the workings of an ion channel.

The lab is currently focusing on understanding how the voltage-dependent gating behavior of sodium channels is modified by gating-modifier toxins and local anesthetics. Sodium channel malfunction has been associated with disease conditions like cardiac arrhythmias and epilepsies. Local anesthetics alleviate these disease states by reducing electrical excitability of the sodium channels. We are using voltage-clamp fluorimetry to map the structural changes in the sodium channels induced by local anesthetics. These studies are expected to provide fundamental insights into the physical mechanisms of gating and modulation of the Na+ channel.

Another area of interest in the lab is to understand how temperature modulates voltage-dependent gating of TRP ion channels. Some members of the TRP family respond acutely either to a heat or to a cold stimulus. Recently, it has been shown that these channels are also voltage-dependent and that temperature affects their voltage-dependent gating. The lab is interested in understanding the biophysical principles that govern temperature dependent gating of these channels using both time-resolved spectroscopic as well as electrophysiological approaches.

Source:  http://neuro.wisc.edu/faculty/chanda.asp