Ion Transport from Physics to Physiology: the Missing Rungs in the Ladder
Mechanisms of Temperature-dependent Gating: Lessons from Designer channels.Baron Chanda
In mammals and high eukaryotes, members of the TRP channel family such as TRPV1 and TRPM8 are largely responsible for mediating thermal sensitivity in peripheral nerves. Despite the fact that multiple high-resolution structures of TRP channels including TRPV1 have been solved in the past few years, the biophysical underpinnings of acute temperature sensitivity remain poorly understood. Using a reverse engineering approach, we have created temperature-sensitive mutants of the Shaker potassium ion channel whose gating is intrinsically temperature-insensitive. Thermodynamic analysis shows that the free energy of channel activation is much more temperature-dependent compared to other well-studied processes such as protein unfolding. Our preliminary analysis suggests that thermal dependence of charge movement plays a unique role in making the designer channels highly temperature-sensitive.