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Hypokalemic periodic paralysis (HypoPP) is a rare genetic disease associated with mutations in CACNA1S or SCN4A encoding the voltage-gated Ca2+ channel Cav1.1 or the voltage-gated Na+ channel Nav1.4, respectively. Most HypoPP-associated missense changes occur at the arginine residues within the voltage-sensing domain (VSD) of these channels. It is established that such mutations destroy the hydrophobic seal that separates external fluid and the internal cytosolic crevices, resulting in the generation of aberrant leak currents called gating pore currents. Presently, the gating pore currents are thought to underlie HypoPP. Here, based on HEK293T cells and by using the Sleeping Beauty transposon system, we generated HypoPP-model cell lines that co-express the mouse inward-rectifier K+ channel (mKir2.1) and HypoPP2-associated Nav1.4 channel. Whole-cell patch-clamp measurements confirmed that mKir2.1 successfully hyperpolarizes the membrane potential to levels comparable to those of myofibers, and that some Nav1.4 variants induce notable proton-based gating pore currents. Importantly, we succeeded in fluorometrically measuring the gating pore currents in these variants by using a ratiometric pH indicator. Our optical method provides a potential in vitro platform for high-throughput drug screening, not only for HypoPP but also for other channelopathies caused by VSD mutations.

In this study, the braking performance of the undulating fin propulsion system of a biomimetic squid-like underwater robot was investigated through free run experiment and simulation of the quasi-steady mathematical model. The quasi-steady equations of motion were solved using the measured and calculated hydrodynamic forces and compared with free-run test results. Various braking strategies were tested and discussed in terms of stopping ability and the forces acting on the stopping stage. The stopping performance of the undulating fin propulsion system turned out to be excellent considering the short stopping time and short stopping distance. This is because of the large negative thrust produced by progressive wave in opposite direction. It was confirmed that the undulating fin propulsion system can effectively perform braking even in complex underwater explorations.