The department of physiology has 8 scientists and 2 administrative staff. While the scientific interests, backgrounds and career paths of faculty are diverse, the whole department is loosely integrated by functioning as a single lab, and shares common scientific interests, as well as resources and techniques. Model systems used for the research include cell lines, zebrafish, frogs, and mice. Lab members study fundamental mechanisms underlying biological phenomena, which can potentially lead to therapeutic innovations. Projects in the department encompass nervous, circulatory, renal and endocrine systems, whose common denominator can be characterized as the “ions and membrane excitability”. Molecules in foci include neurotransmitter/hormone receptors and their downstream molecules, ion channels/transporters and their interacting partners, and synaptic vesicle proteins. We combine genetics, electrophysiology, optics and molecular biology as experimental techniques. Some of the individual, on-going projects in the department are summarized below.
1. Acetylcholine receptors
Dr. Ono studied the nicotinic acetylcholine receptor (AChRs) in the neuromuscular junction (NMJ) over the past two decades using zebrafish as a model system (Daikoku et al., 2015; Egashira et al., 2018). By using mutants and transgenic animals, he made several discoveries including: 1) the active role of AChRs in the synapse formation (Ono et al., 2001; Ono et al., 2004), 2) the regulation of synaptic function by rapsyn (Ono et al., 2002), 3) the regulation of rapsyn transport by the AChR (Park et al., 2012), 4) distinct molecular compositions of AChRs in NMJs of slow and fast muscle fibers (Mongeon et al., 2011; Park et al., 2014), 5) a special mode of synaptic vesicle release in receptor-less NMJs (Mott et al., 2018), and 6) establishment of an animal whose slow muscle fibers selectively receive synaptic inputs (Zempo et al., 2020). We aim to unravel the molecular mechanisms underlying these findings.
2. Gut motility
In collaboration with the Department of Surgery, we analyzed neural network controlling the gut peristalsis. Peristalsis can be either anterograde or retrograde. The neural control of the latter remained enigmatic. Taking advantage of the transparency of zebrafish larvae and the forward genetics, we revealed that HCN4 channel plays a major role in the retrograde peristalsis (Fujii et al., 2020). We continue to analyze neurons expressing this channel.
3. Potassium channels
Dr. Nakajo, who was a lab member and now has an independent lab as a professor of physiology at Jichi Medical College, studied the gating properties of the slow delayed rectifier potassium (IKs) channel (Nakajo & Kubo, 2007, 2014; Nakajo et al., 2011). IKs channel is composed of two subunits, KCNQ1 (pore-forming) and KCNE1 (auxiliary), and both are known as causative genes for cardiac arrhythmia. Collaborative projects continue to study these channels in vivo, using zebrafish genetics.