Nerve cells send their signals encoded in electrical impulses over long distances. Concerted actions of various ion channels are required for properly generating these nerve impulses. Potassium channels are involved at the late phase in an impulse, and its role is to return a nerve cell to a resting state after the impulse has passed through it and gear up for the next one. The Kv1.2 ion channel helps ensure that this process works smoothly.
By experimentally manipulating signal conditions with the new co-culture system, Gu and his colleague were able to establish part of the sequence of events required for myelinated hippocampal neurons to effectively get their signals to their targets. Starting with a protein known to be produced by myelin and axons, called TAG-1, a cell adhesion molecule, they traced a series of chemical reactions indicating that myelin on the hippocampal axons was controlling the placement and activity of the Kv1.2 ion channel.
"The analysis allowed us to see the signaling pathways involving myelin's regulation of the Kv1.2 channel's placement along the axon as well as fine-tuning of the channel's activity," Gu said.
When MS demyelinates these axons, the affected nerve cells don't get the message to rest, and subsequently can't prepare adequately to receive and transmit the next signal that comes along.
"This means a nerve impulse will have a hard time traveling through the demyelinated region," Gu said. "This shows that the ion channel is probably involved in the downstream disease progression of MS."
Gu envisions many additional uses for the new co-culture system, including additional studies of how myelin affects the behavior of other channels, proteins and molecules that function within axons, as well as to screen the effects of experimental drugs on these myelinated cells.
This work was supported by a Career Tr
|Contact: Chen Gu|
Ohio State University