We report that ANO1 (also known as TMEM16A) Ca 2+ -activated Cl − channels in small neurons from dorsal root ganglia are preferentially activated by particular pools of intracellular Ca 2+ . These ANO1 channels can be selectively activated by the G protein-coupled receptor (GPCR)-induced release of Ca 2+ from intracellular stores, but not by Ca 2+ influx through voltage-gated Ca 2+ channels. This ability to discriminate between Ca 2+ pools was achieved by the tethering of ANO1-containing plasma membrane domains, which also contained GPCRs such as bradykinin receptor-2 and protease-activated receptor-2, to juxtamembrane regions of the endoplasmic reticulum. Interaction of the C-terminus and the first intracellular loop of ANO1 with IP 3 R1 (inositol 1,4,5-trisphosphate receptor 1) contributed to the tethering. Disruption of membrane microdomains blocked the ANO1 and IP 3 R1 interaction and resulted in the loss of coupling between GPCR signaling and ANO1. The junctional signaling complex enabled ANO1-mediated excitation in response to specific Ca 2+ signals rather than to global changes in intracellular Ca 2+ .

Large-conductance voltage- and calcium-activated potassium (BK) channels contain four pore-forming α subunits and four modulatory β subunits. From the extents of disulfide cross-linking in channels on the cell surface between cysteine (Cys) substituted for residues in the first turns in the membrane of the S0 transmembrane (TM) helix, unique to BK α, and of the voltage-sensing domain TM helices S1–S4, we infer that S0 is next to S3 and S4, but not to S1 and S2. Furthermore, of the two β1 TM helices, TM2 is next to S0, and TM1 is next to TM2. Coexpression of α with two substituted Cys’s, one in S0 and one in S2, and β1 also with two substituted Cys’s, one in TM1 and one in TM2, resulted in two αs cross-linked by one β. Thus, each β lies between and can interact with the voltage-sensing domains of two adjacent α subunits.

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In recent years, the authors have proposed lightweight exoskeleton designs for upper arm rehabilitation using multi-stage cable-driven parallel mechanism. Previously, the authors have demonstrated via experiments that it is possible to apply "assist-as-needed" forces in all directions at the end-effector with such an exoskeleton acting on an anthropomorphic machine arm. A human-exoskeleton interface was also presented to show the feasibility of CAREX on human subjects. The goals of this paper are to 1) further address issues when CAREX is mounted on human subjects, e.g., generation of continuous cable tension trajectories 2) demonstrate the feasibility and effectiveness of CAREX on movement training of healthy human subjects and a stroke patient. In this research, CAREX is rigidly attached to an arm orthosis worn by human subjects. The cable routing points are optimized to achieve a relatively large "tensioned" static workspace. A new cable tension planner based on quadratic programming is used to generate continuous cable tension trajectory for smooth motion. Experiments were carried out on eight healthy subjects. The experimental results show that CAREX can help the subjects move closer to a prescribed circular path using the force fields generated by the exoskeleton. The subjects also adapt to the path shortly after training. CAREX was also evaluated on a stroke patient to test the feasibility of its use on patients with neural impairment. The results show that the patient was able to move closer to a prescribed straight line path with the "assist-as-needed" force field.