FBS Colloquia No.405Physiological Laboratory

Mathematical models realistically demonstrate the dynamics of ions and small molecules within cells

Research on ion channels has continued to evolve over the past century. In the 1940s, Erlanger, E.J. and Gasser, H.S. identified the mechanism of neural conduction (1944). In the 1950s, Hodgkin, A. and Huxley, A. used the voltage clamp technique on giant squid nerve fibers to study the mechanism by which sodium and potassium currents pass through voltage-gated channels to generate action potentials. Eccles, J. elucidated the inhibitory ion mechanism at central synapses (1963). In the 1970s, the patch-clamp technique developed by Neher, E. and Sakmann, B. enabled the recording of single channel currents (1981), allowing the measurement and analysis of various ion channel currents in diverse cells (the years in parentheses indicate when each researcher received the Nobel Prize in Physiology or Medicine). Even today, electrophysiological methods remain a powerful tool for directly elucidating ion channel function. Meanwhile, recent years have seen the development of computational methods that speculates the dynamics of substances and ions moving across cell membranes, alongside ion channel gating and membrane potential changes, enabling the reproduction of complex phenomena. This colloquium introduces two recent studies using mathematical models to study cellular functions, focusing on ion channels and ion dynamics in cells. First, Takeuchi presents electrophysiological experiments on ligand-gated channels expressed on olfactory cilia and uses a digital model to show how molecular dynamics within a single cilium influence olfaction. Next, Himeno will present simulations of excitation propagation and arrhythmias using a human ventricular myocyte model. We will discuss the role of mathematical models in elucidating cellular excitation mechanisms mediated by ions and ion channels, utilizing an original program developed for this purpose.