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Ion channel gate mechanism is established

LiU researchers have resolved a scientific quandary on the mechanisms for opening and closing cellular ion channels and thereby identified new targets for designer drugs. Epilepsy and arrhythmia are two possible new research areas.

Professor Fredrik Elinder and medical doctor Amir Broomand, researchers in molecular neurobiology, present their findings in the September issue of the prestigious scientific journal Neuron.

Neural signals are transmitted between cells at speeds as high as 100 meters per second. These electrical impulses open and close specialized pores in the cell membrane. This creates a path for the transmission of sodium and potassium ions vital to the functioning of our brain, heart and muscles.

The ion channels have been thoroughly charted. In 2003, the Nobel prize in chemistry was co-awarded to two American scientists: Roderick MacKinnon for structural and mechanistic studies of ion channels, and Peter Agre for the discovery of water channels. MacKinnon mapped the inner structure of an open potassium channel.

To date no one has been able to define the structure of a closed channel, although three models have been presented in the scientific debate.

"But we have experimentally established which of the three hypotheses is correct," says Frederick Elinder, "namely the helical screw model. We demonstrated how the voltage sensor area of the channel bores itself through the channel protein causing the gate at the bottom of the channel to open and close."

The findings of the LiU researchers pave the way for designing drugs to combat neural diseases.

"We now have a target for drugs to relieve migraine, arrhythmia, epilepsy and muscle diseases—all in some way related to the ion channel," explains Professor Elinder.

Several existing drugs achieve their effect by affecting the ion channels. The local anesthetic used by your dentist, for instance, plugs an expanse of channels to block electric impulses.

However, for cardiac and neural surgery the anesthetic must be more specific. Rather than plug an expanse of ion channels, a physician would prefer to influence the opening and closing mechanisms with a drug that controls the gate "hinge". The LiU research findings improves the odds of designing such a drug.

Large-Scale Movement within the Voltage-Sensor Paddle of a Potassium Channel - Support for a Helical-Screw Motion appears in Neuron no. 59, September 11, 2008.


2008-09-30




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Last updated: 2009-06-03