Electrophysiological experiments in microgravity: lessons learned and future challenges

Abstract

Advances in electrophysiological experiments have led to the discovery of mechanosensitive ion channels (MSCs) and the identification of the physiological function of specific MSCs. They are believed to play important roles in mechanosensitive pathways by allowing for cells to sense their mechanical environment. However, the physiological function of many MSCs has not been conclusively identified. Therefore, experiments have been developed that expose cells to various mechanical loads, such as shear flow, membrane indentation, osmotic challenges and hydrostatic pressure. In line with these experiments, mechanical unloading, as experienced in microgravity, represents an interesting alternative condition, since exposure to microgravity leads to a series of physiological adaption processes. As outlined in this review, electrophysiological experiments performed in microgravity have shown an influence of gravity on biological functions depending on ion channels at all hierarchical levels, from the cellular level to organs. In this context, calcium signaling represents an interesting cellular pathway, as it involves the direct action of calcium-permeable ion channels, and specific gravitatic cells have linked graviperception to this pathway. Multiple key proteins in the graviperception pathways have been identified. However, measurements on vertebrae cells have revealed controversial results. In conclusion, electrophysiological experiments in microgravity have shown that ion-channel-dependent physiological processes are altered in mechanically unloaded conditions. Future experiments may provide a better understanding of the underlying mechanisms.

Harnessing the Space Environment for the Discovery and Development of New Medicines

“…The study determined the time-frame of gravity-forced transduction to the transcriptome paying particular attention to cation channel signaling as a point source for mechano-transduction in the absence or presence of the channel inhibitor SKF-96365. The study reported profound alterations in the transcriptome after 20 s exposure to μG or HG and only 2.4% of all μGregulated transcripts were sensitive to the inhibitory effects of SKF-96365 and is consistent with the notion that ion-channel directed biochemical processes are altered in mechanically loaded versus unloaded conditions (Wuest et al 2018).…”

Interactions between Muscle and Bone—Where Physics Meets Biology

“…Mechanosensitive ion channels, which were discussed above as important generators of calcium spikes for osteogenic signals, are altered in µG as shown for neuronal cells or the cells of primitive organisms. Although there are not many data about musculoskeletal systems, one should anticipate that the same holds true for musculoskeletal signal transduction [176]. Many of the genes in the respectively published gene lists remain to be characterized in terms of their functional relevance for mechanotransduction and the maintenance of muscle and bone mass and function.…”

Gravitational Force—Induced 3D Chromosomal Conformational Changes Are Associated with Rapid Transcriptional Response in Human T Cells

“…One robust hypothesis proposed the cytoskeleton as an organized and stabilized tension-dependent gravity-sensing architecture [10], where forces are mediated by both intermediate filaments and F-actin [11,12]. It has been also proposed that mechanosensitive ion channels [13], changes in the cell membranes fluidity [14], transcription factors [15], and transcriptional and translational regulations via noncoding RNA mechanisms [16] are involved in cellular sensitivity to gravity.…”