Commentary: Opening Leads to Closing

Commentary for the October 1, 2018 issue of the Journal of General Physiology (v. 150 art. 1356):

Opening leads to closing: Allosteric crosstalk between the activation and inactivation gates in KcsA

Lucie Delemotte

Voltage-gated potassium (Kv) channels control a number of different physiological processes, including the firing rate in axons. Such K+ channels display a reduction of conductance after exposure to a prolonged activating stimulus. This process, referred to as inactivation, causes repolarization of the cell membrane after the depolarizing phase of an action potential. The transient openings that result from it also allow neurons to readily fire a new action potential. Two types of inactivation mechanisms have been described in Kv channels (Hoshi et al., 1990). Fast inactivation, also called N-type inactivation, results from a mechanism that has been ascribed to pore blocking by a N-terminal peptide. Slow inactivation, or C-type inactivation, is revealed upon suppression of fast inactivation and is thought to be due to a conformational change occurring within the pore of the channel. While the structural basis of C-type inactivation appears to have been established, how it is dynamically coupled to channel activation remains to be understood in detail. In the Journal of General Physiology, a new study (see Li et al. 2018) proposes an intriguing mechanism for the allosteric control of C-type inactivation by the activation gate in the bacterial K+ channel KcsA.

Read the full commentary here.