A group of researchers from the Institute of Neurosciences, joint center of the Miguel Hernández (UMH) in Elche and the Higher Council for Scientific Research (CSIC), has developed a study to identify which proteins interact with the synaptic receptors. The work, which explains the characteristics of the transmission of information between neurons, has been published in the latest issue of the «Journal of Neuroscience».
Transmitting information between neurons in the synapses happens, a link connection or packed intercellular receptors that can be activated by chemical neurotransmitters, such as glutamate. A glutamate receptor is called kainate, which forms an ion channel whose activation when glutamate is released, excites neurons. Kainate receptors belong to the family inotropic, forming channels ionésicos but, unlike other inotropic receptors family, kainate receptors can activate an alternative path that inhibits calcium channel, decreases the release of brain neurotransmitters and blocking the membrane repolarization, which causes also neuronal excitation.
The researcher Juan Lerma explained that «this peculiarity of kainate receptors is an alternative route, not canonical, of neuronal excitation that our research group described a few years ago. We realized that some of the activities of the kainate produced activation of other proteins such as phospholipase C and could be prevented with the pertussis toxin, indicating that the action of kainate receptors was mediated by activation of G proteins, which are proteins signal transducers «.
For its part, the researcher of the Institute of Neurosciences Sergio Valbuena said that «this research has opened new perspectives on the classic concept of the signaling kainate receptors, but left open a mystery: how is active and which elements are involved? «. To answer this question, researchers at the Neurosciences Institute have carried out a proteomic study of mouse brain extracts, which has allowed them to identify proteins that interact with the intracellular portion of the kainate receptor subunits, the GluK1. Thus, they have been identified to 22 interacting proteins specifically with this receptor, including the alpha subunit of the protein is Go. With a series of additional experiments, these researchers have shown that protein Go is activated upon stimulation of this receptor and, through the use of genetically modified mice have shown that this activation depends exclusively on the presence of the receptor subunit GluK1 kainate.
«This non-canonical signaling kainate receptors is involved in altering the balance between excitation and inhibition in the nervous system, upon which the right brain function,» said the researcher at the Institute of Neurosciences Isabel Aller. Also, the researcher Juan Lerma added that «our work has provided the key to the development of drugs capable of discriminating between the two signaling systems, improving our ability to modulate the brain activity of a fine way. In the future, we could even design small peptides that disrupt the coupling between the kainate receptor and G protein to control their blocking action of synaptic inhibition or, for example, to control the neuronal repolarization sometimes can cause hyperexcitability and developing epilepsy. «