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Capturing clues to the molecular mechanism that enables the rapid onset of action potential
Ayumi Sumino1 (Takashi Sumikama1, Katsumasa Irie2)

Action potentials, generated by the opening and closing of ion channels, are essential for biological activity. For example, electrocardiograms and electroencephalograms are recordings of action potentials in the heart and brain, respectively. Action potentials were first recorded in 1939, and their rapid onset has been thought to be related to the cooperative opening of Na+ channels (ion channels that mainly pass Na+ ions), but the molecular mechanism of the cooperative opening is still unknown. In this study, by using high-speed atomic force microscopy, which can visualize molecular motions, we have shown that the voltage sensors (VSD) of Na+ channels dissociate from the pore domains in the closed state (left figure), and dissociated VSDs interact each other and make dimers. Theoretical calculations have revealed that such networks of interactions can be formed in real neurons. These interaction networks are considered to be simultaneously cut to open the Na+ channels to generate action potentials. This mechanism is a potential candidate for the molecular mechanism of cooperative opening, which has remained unexplained for more than 80 years.

Ayumi Sumino, Takashi Sumikama, Mikihiro Shibata, Katsumasa Irie. Voltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state. Nature Communications 14: 7835, 2023.

<Figure Legends>
Schematic diagram of the network formed by closed Na+ channels (left) and open Na+ channels (right).

1Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Japan
2Department of Biophysical chemistry School of Pharmaceutical Science, Wakayama Medical University, Japan