Description: The resting membrane conductance of mammalian skeletal muscle is controlled by a chloride channel called CLC-1, one of the muscle-type CLC family members. Mutation of this chloride channel results in congenital myotonia, which is characterized by muscle stiffness and related muscle discomfort. The pathophysiology how a mutation of the channel protein results in channel malfunction is not well understood. Our lab is working on the structures and functions of CLC chloride channels. Besides CLC-1, other CLC family members such as CLC-0 and CLC-5 are under rigorous investigations. We combine electrophysiological recording methods (such as patch-clamp techniques) and fluorescence imaging methods (such as fluorescence resonance energy transfer) to examine the structures and functions of these channel protein molecules.

Duration:Long term

Several references for the medical students to read to determine if they might be interested in the project:

1. Chen M.-F. and Chen T.-Y. (2003) Side-chain charge effects and conductance determinants in the pore of ClC-0 chloride channel. J. Gen. Physiol. 122: 133-145.
2. Lin C.-W. and Chen T.-Y. (2003) Probing the pore of ClC-0 by substituted cysteine accessibility method using methane thiosulfonate reagents. J. Gen. Physiol. 122: 147-159.
3. Chen T.-Y. (2003) Coupling gating with ion permeation in ClC chloride channels. Science STKE. 2003: pe23.
4. Chen T.-Y. (2005) Structure and function of ClC channels. Ann. Rev. Physiol. 67: 809-839.