所長招聘セミナー

Physico-chemical fundamentals of ion channel structure and function are critically important for understanding their integration into molecular ensembles to build up living cells and whole body, in health and disease. Plasmalemmal ion channels conduct inorganic ions (Na+, K+, Ca2+ and Cl–) and control excitability and contraction. However, they may also pass some other charged molecular species, a feature largely unexplored at present for most of ion channels. Our original nonelectrolyte partitioning method (NPM) revealed unexpectedly wide pores of two types of volume-regulated anion channels, the maxi-anion and the volume-sensitive outwardly rectifying (VSOR) Cl– channel. We found that the maxi-anion channel provides a pathway for release of ATP in kidney, heart and brain to initiate tremendously important downstream purinergic signaling. A narrower pore of VSOR Cl–-channel served as a path for release of excitatory glutamate, which mediates astrocyte-to-neuron signaling, and tripeptide glutathione, which is an important determinant for cellular redox state and γ-glutamyl cycle. Thus, we proposed a new concept of channel-mediated metaboergic (metabolite-mediated) cell-to-cell signaling. The CFTR pore was also wide to take part in such events. The maxi-anion and VSOR Cl– channel proteins remain unidentified. The promising ways of their molecular identification, as well as future directions of channel reconstitution in physico-chemically defined systems, localization by smart-imaging-patch-clamp, pharmacology, channel manipulations for nanobiology and nanomedicine, and channel integration to cellular and brain functions will be discussed.