News Editor: Renato M.E. Sabbatini, PhD
As many of us know to our cost, a few drinks can have dramatic effects on both the brain and the body – slowing
thought and reactions, for example. But exactly how alcohol exerts its effects has been hazy. Now researchers show
that it can directly affect vital molecules, called 'ion channels', on the surfaces of brain cells.
Different kinds of ion channels control all the activities of neurons, by allowing controlled amounts of positively or negatively charged ions in and out of cells. This causes the electrical activity of the neurons to go up or down and can have profound effects on the workings of the brain. Normally, ion channels are opened or closed by specific chemicals called 'neurotransmitters' or by changes in the voltage difference between the inside and outside of the neuron.
Toru Kobayashi of Niigata University, Japan, and Joanne Lewohl of the University of Texas at Austin, and their colleagues have discovered that alcohol can cause a particular type of ion channel, called a 'GIRK' (short for 'G-protein coupled inwardly rectifying potassium channel'), to open. When GIRK is open potassium ions can leave, thereby reducing the activity of neurons. This phenomenon, described in Nature Neuroscience1, could explain why alcohol seems generally to depress brain function.
Kobayashi's group has shown that mice with mutations in the genes for GIRK channels, called 'weaver' mice, react differently to alcohol than normal mice. In particular, the weaver mice are not susceptible to the usual painkilling effect of a dose of ethanol. This suggests that alcohol normally reduces pain by opening the GIRK receptors. However, other effects of alcohol are unchanged in weaver mice. For example, alcohol still causes their heart rates to slow – so this must happen through another mechanism. The most likely explanation is that alcohol influences heart rate through a different type of ion channel.
It was already known that alcohol could interfere with the normal working of other ion channels in various areas of the brain, including those responsible for controlling movement. In these cases, however, it has always been necessary for something else – such as a neurotransmitter or a change in the electrical activity of the neuron – to cause the ion channel to open or close. It was thought that alcohol could only alter the normal opening or closing reactions of the channels – but now it appears to be able to open GIRK channels, at least, all by itself.
Source: Kobayashi, T., Ikeda, K., Kojima, H., Niki, H., Yano, R., Yoshioka, T. & Kumanishi, T. Ethanol
opens G-protein-activated inwardly rectifying K+ channels Nature Neuroscience 2, 1091 - 1097 (1999)