Baron Chanda

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The objective of my 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. We use 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.

We are 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. We are interested in understanding the biophysical principles that govern temperature dependent gating of these channels using both time-resolved spectroscopic as well as electrophysiological approaches.

Selected Publications

• Chowdhury, S., and Chanda, B.^d (2010) Deconstructing thermodynamic parameters from site-specific observables in a coupled system. Proceedings of the National Academy of Sciences (USA) 107(44), 18856-18861 (Track II submission).
• Arcisio-Miranda, M., Muroi, Y., Chowdhury, S., and Chanda, B.^d (2010) Molecular basis of allosteric modification of voltage-dependent gating by local anesthetics. Journal of General Physiology 136(5), 541-554
• Wang, D., Zhang, Z., Chanda, B., and Jackson, M. (2010) Improved probes for hybrid voltage sensor imaging. Biophysical Journal 99, 2355-2366
• Muroi, Y., Arcisio-Miranda, M., Chowdhury, S., and Chanda, B.^d (2010) Molecular determinants of coupling between the domain III voltage-sensor and pore of a sodium channel. Nature Structural and Molecular Biology 17, 230-237
• Muroi, Y., and Chanda, B.^d (2009) Local anesthetics disrupt energetic coupling between voltage-sensors of the sodium channel. Journal of General Physiology 133, 1-15
• Campos, F., Chanda, B., Baeiro, P., and Bezanilla, F. (2008) a-scorpion toxin impairs a conformational change that leads to fast inactivation of the sodium channels. Journal of General Physiology 132, 251-62
• Kumari, S., Borroni, V., Chaudhary, A., Chanda, B., Massol, R., Mayor, S., and Barrantes, F.J. (2008) The nicotinic acetylcholine receptor is internalized via a rac-dependent, dynamin-independent endocytic pathway. Journal of Cell Biology 181, 1179-1193
• Chanda, B. and Bezanilla, F. (2008) A common pathway for charge transport through voltage-sensing domains. Neuron 57, 345-351
• Campos, F., Chanda, B.^d, Baeiro, P., and Bezanilla, F.^d (2007) b-scorpion toxin modifies gating transitions in all four voltage-sensors of the sodium channel. J. Gen. Physiol. 444(7115), 10.1085/jgp.200609719.
• Ben-Chaim, Y., Chanda, B., Bezanilla, F., Dascal, N., Parnas, I. and Parnas, H. (2006) Movement of “gating charge” is coupled to ligand binding in a G-protein coupled receptor. Nature 444(7115), 106-109.
• Bannister, J.P., Chanda, B., Bezanilla, F., and Papazian, D.M. (2005) Optical detection of rate-determining, ion-modulated conformational changes of the ether-a-go-go K+ channel voltage sensor. Proc. Natl. Acad. Sci. (USA) 102(51),18718-19723.
• Chanda, B.*, Blunck, R.*, Faria, L.C., Schweizer, F.E., Mody, I. and Bezanilla, F. (2005) A hybrid approach to measuring electrical activity in genetically specified neurons. Nature Neuroscience 8 (11), 1619-1626.
• Chanda, B., Asamoah, O.K., Blunck, R., Roux, B. and Bezanilla, F. (2005) Gating charge displacement in voltage-gated ion channels involves limited transmembrane movement. Nature 436(7052), 852-836.
• Chanda, B.*, Asamoah, O.K.*, and Bezanilla, F. (2004) Coupling interactions between voltage sensors of the sodium channel as revealed by site-specific measurements. J. Gen. Physiol. 123, 217-230.
• Chanda, B. and Bezanilla, F. (2002) Tracking voltage-dependent conformational changes in skeletal muscle sodium channel during activation. J. Gen. Physiol. 120, 629-645.

* = Equal contribution
d = Corresponding authors