Ion channels: touch at the molecular level.

Ion channels: Touch at the molecular level

When an object presses into your skin --be it a pencil you just picked up or a hand gripping your arm--sensory nerves send a message to your brain. But what exactly sets these nerves firing? Scientists are now analyzing specific pores, or channels, through cell membranes that may be responsible for touch perception, hearing and balance, as well as for the body's regulation of blood pressure, lung inflation, gut distension and other physiological processes.

The idea that mechanical pressure alters membrane channels, which in turn trigger a nerve impulse, has been around for decades. But Frederick Sachs and Falguni Guharay of the State University of New York at Buffalo are the first to find a channel that is directly activated by mechanical stress. This channel, through which charged atoms (ions) pass, was discovered not in nerve cells but in chick muscle cells grown in laboratory culture. The scientists suggest that it may be a prototype for the wide variety of specialized mechanoreceptors in the body.

"The nervous system has lots of ion channels,' says David Corey of Massachusetts General Hospital in Boston, who has studied mechanisms of hearing and balance. "Some [channels] are activated by voltage, some by chemicals. What is especially significant about the work on mechanical sensation is that it represents a third class of ion channel proteins.'

Sachs and Guharay activate the newly discovered channel, which they call the stretch-activated channel, by applying suction to a thin glass pipette attached to the cell membrane. With this method, they have been able to observe the activity of a single channel.

"The ion channel normally opens and shuts randomly,' explains Sachs. "Applying pressure biases it to be open more often. And when it's open more often, you get more current flow that ends up stimulating the nerve, and the impulse goes to the brain.'

Sensitivity to membrane tension is not characteristic of all ion channels, Sachs says. The scientists have examined several other types of channels that do not show this characteristic.

Among their findings are that activation increases the flow of potassium and sodium ions through the stretch-activated channel, with potassium flowing twice as fast as sodium. They also find that the probability of the channel being open increases exponentially with the square of the membrane tension applied. They propose from these kinetics that the channel has three closed states and one open state. The scientists present further details in the June JOURNAL OF PHYSIOLOGY.

The energy for controlling the channel probably comes from the mechanical force applied. Sachs and Guharay observed that channels in isolated pieces of membrane, with no chemical energy sources, continue to show activity. They hypothesized that the channel is a cylindrical plug of protein transversing the membrane. They then calculated that it would take an enormous molecule to be sufficiently distorted by membrane tension to control the channel. Therefore, the scientists speculate that a cell's network of filaments, the cytoskeleton, serves as "strings' between the stretch-activated channel and distant points on the membrane. These filaments gather force from a large area and convey it to the channel.

The role of this channel in the muscle cells where it has been observed is not yet known. There is evidence that it is also present in some other cells, including nerve and heart cells. But the stretch-activated channel has not been found in some of the other cells examined.

Sachs says that it is now important to look at the specialized mechanoreceptor cells of the body to see how they detect distortion. "I think we now know which questions to ask,' he says. "There is little doubt that research on mechanoreception is entering a renaissance.'