This Research Topic is part of the Nicotinic Alpha9 and Alpha10 Subunits: Ancient Receptors in Modern Times and Modern Places series:
Nicotinic Alpha9 and Alpha10 Subunits: Ancient Receptors in Modern Times and Modern PlacesNicotinic acetylcholine receptors (nAChRs) are ion-gated channels that have diverse function in nervous and non-nervous tissues. The a9 and a10 subunits are members of the subfamily I, epithelial ion-gated nicotinic receptor gene family. These subunits are the most recently discovered (and perhaps the last to be discovered) nAChR subunits in mammals but are phylogenetically the oldest.
The a9 and a10 subunits are not expressed in the normal mammalian brain, making them unique among nAChRs. They were first localized in cochlear hair cells. As a consequence of their discovery in hair cells, the focus of study of these subunits has largely been on their function in the cochlea.They are localized at postsynaptic sites in hair cells, where they mediate the neurotransmitter actions of acetylcholine (ACh). They have important functions during development and in the protection of the ear from damaging noise. Darwinian evolutionary changes in the mammalian a10 subunit resulted in increased calcium permeability and parallels the evolution of the anion chloride transporter SLC26A5 (prestin) and somatic electromotility in cochlear OHCs. The mammalian a10 subunit, unlike the avian a10 subunit, does not form homomers when expressed in oocytes. There is an emerging literature that the distribution of the a9 and a10 subunits in peripheral tissues is widespread and non-synaptic, regulated in disease states, and may not always be assembled as heteromeric receptors. One or both subunits are expressed in most immune cells, dorsal root ganglion, keratinocytes, brain glioblastoma, lung, colon, human breast cancer. Their expression levels may be prognostic in cancer and osteoporosis, and recent evidence suggests they may be involved in immune regulation. Importantly, they are potential targets for treatment of pain, cancer, and inflammatory diseases.
Despite the recent upsurge in research interest in these subunits, there is much unknown about their functions and the underlying molecular mechanisms. They are most similar to the a7* nAChR; a-bungarotoxin and strychnine are antagonists of a7* and a9* receptors and a7* and a9* highly permeable to calcium. Recent evidence suggests a functional interaction of the subunits and potentially a structural association.
In the first volume of this Research Topic, we covered the current state of basic research activities on the a9 and a10 receptor. In particular ideas about their roles in basic biology, physiology and inflammation and animal models for analysis of functions and human disease states dominated the submitted manuscripts. In the second volume, we encourage manuscripts that extend and expand those areas, continuing to report advances in basic research, pain, glioblastoma, cancer, as well as new research on the nasal epithelium and lung potentially related to Covid-19. Studies on the effects of peripheral a9 and a10 receptors on brain mechanisms are also encouraged, such as the changes in auditory brain areas resulting from altered cochlear efferent hair cell activity. We will welcome critical Reviews and Commentary on therapeutic potential and clinical interest in addition to Original Research papers.