Cutaneous Sensitivity Across Regions of the Foot Sole and Dorsum are Influenced by Foot Posture

Understanding the processing of tactile information is crucial for the development of biofeedback interventions that target cutaneous mechanoreceptors. Mechanics of the skin have been shown to influence cutaneous tactile sensitivity. It has been established that foot skin mechanics are altered due to foot posture, but whether these changes affect cutaneous sensitivity are unknown. The purpose of this study was to investigate the potential effect of posture-mediated skin deformation about the ankle joint on perceptual measures of foot skin sensitivity. Participants (N = 20) underwent perceptual skin sensitivity testing on either the foot sole (N = 10) or dorsum (N = 10) with the foot positioned in maximal dorsiflexion/toe extension, maximal plantarflexion/toe flexion, and a neutral foot posture. Perceptual tests included touch sensitivity, stretch sensitivity, and spatial acuity. Regional differences in touch sensitivity were found across the foot sole (p < 0.001) and dorsum (p < 0.001). Touch sensitivity also significantly increased in postures where the skin was compressed (p = 0.001). Regional differences in spatial acuity were found on the foot sole (p = 0.002) but not dorsum (p = 0.666). Spatial acuity was not significantly altered by posture across the foot sole and dorsum, other than an increase in sensitivity at the medial arch in the dorsiflexion posture (p = 0.006). Posture*site interactions were found for stretch sensitivity on the foot sole and dorsum in both the transverse and longitudinal directions (p < 0.005). Stretch sensitivity increased in postures where the skin was pre-stretched on both the foot sole and dorsum. Changes in sensitivity across locations and postures were believed to occur due to concurrent changes in skin mechanics, such as skin hardness and thickness, which follows our previous findings. Future cutaneous biofeedback interventions should be applied with an awareness of these changes in skin sensitivity, to maximize their effectiveness for foot sole and dorsum input.

The extracellular loop of the auxiliary β1-subunit is involved in the regulation of BKCa channel mechanosensitivity

The large conductance Ca2+-activated potassium (BKCa) channel is activated by stretch. The stress-regulated exon (STREX) in α-subunits is known to affect the mechanosensitivity of BKCa channels. However, in human colonic smooth muscle cells (HCoSMCs), we found that the α-subunits without STREX (ZERO-BK) and β1-subunits could be detected yet the cells were mechanosensitive. Whether the β1-subunit is involved in the regulation of BKCa mechanosensitivity is unclear. In the present study, ZERO-BK and β1-subunits were individually expressed or coexpressed in HEK293 cells and cell-attached patch-clamp techniques were used to measure BKCa currents defining mechanosensitivity. Single-channel patch-clamp recordings from HEK293 cells cotransfected with ZERO-BK and β1-subunits showed stretch sensitivity, but there was no mechanosensitivity in HEK293 cells transfected only with ZERO-BK. We also showed that expression of the β1-subunit could increase mechanosensitivity of the STREX-type α-subunits (STREX-BK). To identify the domain in β1-subunits responsible for affecting stretch sensitivity, we expressed β1- LoopDel (chimeric β1-subunits without the extracellular loop) or β1- C TermDel (chimeric β1-subunits without COOH terminus) with ZERO-BK in HEK293 cells. The data showed that deletion of the extracellular loop but not the COOH terminus of β1-subunits virtually abolished the mechanosensitivity. These results suggest that the extracellular loop of the β1-subunit is involved in the regulation of BKCa channel mechanosensitivity and that role is independent of STREX.

A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle

Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching 1.5 µm diameter and 3.2 µm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this defines an ordered sarcomere morphogenesis process under precise transcriptional control – a concept that may also apply to vertebrate muscle or heart development.

Systematic transcriptomics reveals a biphasic mode of sarcomere morphogenesis in flight muscles regulated by Spalt

Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. To study how sarcomeres are built, we performed transcriptome sequencing of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, two clusters are strongly enriched for sarcomeric components. Temporal gene expression together with detailed morphological analysis enabled us to define two distinct phases of sarcomere development, which both require the transcriptional regulator Spalt major. During the sarcomere formation phase, 1.8 μm long immature sarcomeres assemble myofibrils that spontaneously contract. During the sarcomere maturation phase, these sarcomeres grow to their final 3.2 μm length and 1.5 μm diameter and acquire stretch-sensitivity. Interestingly, the final number of myofibrils per flight muscle fiber is determined at the onset of the first phase. Together, this defines a biphasic mode of sarcomere and myofibril morphogenesis – a new concept that may also apply to vertebrate muscle or heart development.