Unravelling the Impact of Microgravity on Calcium Ion Signaling and Sensorium in Spaceflight

Human spaceflight in microgravity induces profound physiological adaptations, yet its effects on the sensory system remain comparatively underexplored. While musculoskeletal and cardiovascular changes are well documented, sensory alterations pose equally important challenges to astronaut safety, performance, and post-mission recovery. Calcium ions (Ca2+), as universal intracellular messengers, play central roles in sensory transduction, neurotransmitter release, and adaptive signaling across all sensory modalities. Emerging evidence suggests that microgravity may influence Ca2+ homeostasis and Ca2+-dependent cellular processes, potentially affecting the functional integrity of sensory pathways. In this review, we synthesize current findings on the impact of microgravity on Ca2+-dependent processes in the five classical senses. Evidence from spaceflight studies, ground-based analogs, and related physiological models suggests possible alterations in taste receptor signaling, Ca2+-binding protein expression, mechanotransduction pathways, and vestibular function. However, direct evidence for microgravity-induced disruption of Ca2+ signaling remains limited for several sensory modalities. Collectively, these changes are associated with altered taste and smell perception, visual disturbances, reduced tactile sensitivity, and vestibular imbalance. By integrating both direct evidence and mechanistic hypotheses across sensory systems, this review highlights Ca2+ signaling as a potential unifying mechanism underlying sensory adaptation to microgravity. We further identify key knowledge gaps and discuss potential directions for developing targeted countermeasures aimed at preserving sensory function during long-duration missions. Beyond spaceflight, these insights contribute to a broader understanding of Ca2+-mediated sensory physiology under extreme environmental conditions.