To understand the effect of a particular mutant protein, whose individual amino acid residue has been, mutated it has to be passed through the ion channel protein and examine the effect that these mutations have on the channel's function. But it is a very laborious process. Hence the new high-throughput screening methodology has come to our rescue which has the ability to analyze 14,000 mutants. The scientists have isolated five mutants that specifically affect menthol activity.
The results were published in the journal Nature Neuroscience. This new understanding could lead to potential advances in pain therapy. This new methodology can be used to study the activation mechanism of other drugs and proteins. Ardem Patapoutian, associate professor at Scripps Research, who directed the research, said that it is understood that our ability to sense temperature is closely linked to our ability to sense pain.Hence if there is a misregulation of temperature-activated ion channels then it can result in chronic pain syndromes. Ion channels are proteins found in the cell membrane that can form a tunnel or channel that allows specific ions to move across the membrane. When activated, the channel opens, allowing an influx of calcium ions into the axon, an electrical signal that alerts the neuron, which relays the message to the brain.
Some of these ion channels are considered as targets to treat chronic inflammatory and neuropathic pain indications. The researchers identified the exact point at which the menthol interacted and the site that translates binding information to ion channel activity.
Research Associate Michael Bandell, said that this could prove to be useful as a general method to analyze the mechanism by which drugs can activate or inhibit ion channels or other receptors. Specifically, the new methodology could be used to identify amino acid residues in certain ion channel proteins and G-protein coupled receptors that are involved in the interaction with small molecules that affect their function.
