Chloride channels render nerve cells more excitable

Apr 20, 2010
3-D reconstruction of a nerve cell from the cerebral cortex (filled with red fluorescent dye). ClC-2 chloride channels may allow the nerve cells to manipulate their own excitability, enabling them to selectively influence intercellular communication. Image: Max Planck Institute of Neurobiology, Martinsried

(PhysOrg.com) -- Nerve cells communicate with each other by means of electrical impulses. To create such an impulse, the cells exchange charged ions with their environment. However, the role played by the ever-present chloride channels remained obscure, although some theories predicted a relation between the chloride channel ClC-2 and epilepsy.

Scientists at the Max Planck Institute of Neurobiology in Martinsried were now able to confirm a number of assumptions about the ClC-2 channel and could at last explain why the anticipated epileptic seizures do not occur when lack the ClC-2 channels in mice. The results also provide a completely new understanding of how nerve cells may actively influence the exchange of information. (The Journal of Neuroscience online publication, April 1st, 2010)

The cell membranes of nerve cells, like those of all other cell types in the body, are perforated by so-called . These permit the exchange of negatively charged chloride ions between the cell and its environment. Yet scientists could so far only speculate about the purpose of this exchange. According to one very prevalent theory, the excitability of nerve cells decreases when they lose chloride ions through these channels. Or, to put it the other way round, the lack of chloride channels would cause nerve cells to become overexcited. This in turn should lead to an increased rate of . However, mice whose nerve cells lack chloride channels due to a genetic mutation were found no more susceptible to epilepsy than healthy animals. And so the function of the ClC-2 and of other chloride channels remained obscure.

Scientists at the Max Planck Institute of Neurobiology have now tracked down a number of the ClC-2 channel's functions. This constitutes the first tangible proof of the circumstances under which chloride ions can escape from nerve cells through the ClC-2 channels. In the case that nerve cells were lacking the ClC-2 channels due to a mutation in the channel's gene, the concentration of chloride inside the cells did indeed increase considerably.

The Max Planck scientists were also the first to successfully prove the third hypothesis - that the nerve cells of mice with a genetic ClC-2 deficiency were much easier to excite than nerve cells in a healthy brain. Earlier assumptions therefore turned out to be correct. Then why did animals lacking the ClC-2 channels show no sign of epilepsy?

The answer to this question was not only plausible, but also straightforward. In addition to having cells that transmit information to their neighbouring cells, the nervous system contains a second group of nerve cells. These cells inhibit the exchange of information between its neighbours. In animals with a ClC-2 genetic defect, these inhibitory nerve cells also forfeit their chloride channels, and therefore become more excitable. Thus, excitatory and inhibitory cells become more excitable. "Although the whole system becomes more sensitive, at the end of the day the balance between the cells is maintained", explains Valentin Stein, leader of the study. And so the anticipated connection between genetic defect and epilepsy is not expressed. However, the lack of ClC-2 channels throws the nervous system into an unnaturally excited state. The scientists therefore speculate that although a defective ClC-2 gene does not cause epilepsy in itself, it may increase the risk of contracting if other factors are present.

"We reckon, however, that we have come across something even more exciting", says Valentin Stein. The neurobiologist is referring to the discovery that nerve cells can theoretically use the ClC-2 channels to influence their own excitability. "If a nerve cell can control its own excitability by opening or closing its ClC-2 channels, then it could basically have a say in whether or not it transmits information to its neighbour." This possibility adds a whole new dimension to brain research. When and how nerve cells transmit information is one of the most fundamental functions of the brain and forms the basis of our ability to think. And so it comes as no surprise that the scientists can hardly wait to get on with the next stage of their investigations into this discovery.

Explore further: Neurons can be reprogrammed to switch the emotional association of a memory

More information: Ilka Rinke, Judith Artmann, Valentin Stein, ClC-2 voltage-gated channels constitute part of the background conductance and assist chloride extrusion, The Journal of Neuroscience, online publication, 01 April 2010

add to favorites email to friend print save as pdf

Related Stories

Light switches for nerve cells

Apr 06, 2010

(PhysOrg.com) -- It sounds like a neurobiologist’s dream: a light-switch that allows nerve cells to be switched on and off at will. Three scientists have found just such a light switch and are now being ...

Complex channels

Jan 24, 2007

The messages passed in a neuronal network can target something like 100 billion nerve cells in the brain alone. These, in turn communicate with millions of other cells and organs in the body. How, then, do whole cascades ...

Milestone in the regeneration of brain cells

Aug 20, 2007

The majority of cells in the human brain are not nerve cells but star-shaped glia cells, the so called “astroglia”. “Glia means “glue”, explains Götz. “As befits their name, until now these cells have been regarded ...

Possible link between different forms of epilepsy found

Jun 16, 2008

Carnegie Mellon University neuroscientists have identified what may be the first known common denominator underlying inherited and sporadic epilepsy — a disruption in an ion channel called the BK channel. Although BK channels ...

Recommended for you

Emotional adjustment following traumatic brain injury

Oct 24, 2014

Life after a traumatic brain injury resulting from a car accident, a bad fall or a neurodegenerative disease changes a person forever. But the injury doesn't solely affect the survivor – the lives of their spouse or partner ...

New ALS associated gene identified using innovative strategy

Oct 22, 2014

Using an innovative exome sequencing strategy, a team of international scientists led by John Landers, PhD, at the University of Massachusetts Medical School has shown that TUBA4A, the gene encoding the Tubulin Alpha 4A protein, ...

User comments : 0