He and his colleagues studied an ion channel that controls neuronal activity called Kv2.1, a type of voltage-gated potassium channel that is found in every neuron of the nervous system.
“Our work showed that this channel can exist in millions of different functional states, giving the cell the ability to dial its activity up or down depending on the what’s going on in the external environment,” said Trimmer. This regulatory phenomenon is called ‘homeostatic plasticity’ and it refers, in this case, to the channel protein’s ability to change its function in order to maintain optimal electrical activity in the neuron in the face of large changes within the brain or the animal’s environment. “It’s an elegant feedback system,” he added.
Using this technique, postdoctoral fellow Kang-Sik Park revealed 16 sites where the protein is modified by the cell by via addition of a phosphate group. Further study–in which each of the sites is removed to reveal its role in modulation– followed by careful biophysical analyses of channel function by postdoctoral fellow Durga Mohapatra, revealed that seven of these sites were involved in the regulation of neuronal activity. Since each site can be regulated independently on the four channel subunits, the neuron can generate a huge (>1018) number of possible forms of the channel.
Using this mechanism, Kv2.1 channels are quickly modified, even mimicking the activity of other potassium ion channels. “The beauty of doing it with a single protein is that it is already there and can change in a matter of minutes. It would take hours for the cell to produce an entirely different potassium channel,” Trimmer explained.
Based on these results, Trimmer and his colleagues hypothesize that parts of the Kv2.1 channel protein interact in ways that make it either easier or harder for it to change from closed to open. The protein, they believe, can exist in either loose states that require low amounts of energy, or voltage, to change from one state to another or a locked-down state that requires lots of energy (high voltage) to open or close. The number and position of phosphate molecules are what determine the amount of voltage required to open the channel.
It just makes intuitive sense. It appeals to my aesthetic sense as well. And it is a great example of the power of evolution.