DATE2023.11.30 #Press Releases
Regulating voltage-gated ion channels
A unique ion channel modulation mechanism could help design ion channel-targeted drugs with fewer side effects.
Nov 30, 2023
Voltage-gated ion channels undergo changes, such as gate opening and closing, by forming molecular complexes with regulatory subunits. The ion channel modulation fine-tunes the channel gating properties leading to unique physiological functions. Such ion channels are involved in neurons and muscle cell activities. So understanding the structure and mechanisms of the ion channel modulation will help design drugs targeting them.
An international collaboration of researchers, led by Osamu Nureki’s team at the University of Tokyo, has now revealed the 3D structure of the Slo1-LRRC channel and its regulatory subunit called γ1. The researchers used electrophysiological analysis to show the unique mechanism by which the regulatory subunit controls both the voltage potential and the calcium-dependent components of the human Slo1-LRRC channel, which plays a role in the secretion of various active substances.
The novel mechanism of ion channel modulation of both calcium sensitivity and voltage by the regulatory subunit could help elucidate the structural basis of ion channels. This knowledge can also lead to therapeutics against ion-channel-related diseases such as epilepsy and heart diseases.
Figure: Schematic of Slo1-LRRC26 complex structure and modulation by LRRC26. LRRC26 interacts with transmembrane and intracellular domain to modulate voltage- and Ca2+-sensitivity of Slo1.
For more details, please read the article:
Daichi Yamanouchi, Go Kasuya, Koichi Nakajo, Yoshiaki Kise, and Osamu Nureki 2023. Dual allosteric modulation of voltage- and calcium-sensitivity of Slo1-LRRC channel complex. Molecular Cell. DOI: 10.1016/j.molcel.2023.11.005