What causes inactivation of an ion channel?

Voltage-gated ion channels (VGICs) are proteins that form a pore in a cell membrane. The pore allows ions to pass through. Neurons and muscle cells receive electric signals through VGICs. VGICs can be activated/open, resting/closed or inactivated/closed. Scientists as St. Jude wanted to understand how a VGIC called Kv4 transitions between states and becomes inactivated.

Little is known about how Kv4 becomes inactivated. So, the scientists focused their work on the mechanism involved. They used a technique called cryogenic electron microscopy.  

Results showed that the mechanism behind Kv4 inactivation involves a symmetry breakdown. Kv4 is composed of four identical copies of a protein. These copies usually adopt the same conformation (shape). Imagine them like a four-leaf clover. However, in inactivated Kv4, each of the two pairs facing each other have different conformations.

This mechanism is distinct from other VGICs. However, the approaches used to understand it could apply to other ion channels.

 “We were able to capture multiple states of this specific ion channel to get a better picture of how this protein works in molecular detail,” said Chia-Hsueh Lee, PhD, Structural Biology.

The findings appeared in Molecular Cell.

Read the press release