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This is a Quantitative Study study.

September 23, 2025Open Access

Hypergravity Enhances Stretch Sensitivity in Rat Cardiomyocytes via Increased Expression and Activity of Stretch-Activated Channels

Key Points

Chronic exposure to hypergravity significantly increases the expression of specific mechanosensitive channels in rat cardiomyocytes.
Notable changes included a 239.48% increase in Traak/K2P4.1 and a 68.23% increase in Trpc1, affecting calcium signaling.
Functional assessments revealed a dramatic hypersensitivity of stretch-activated currents in cardiomyocytes under hypergravity conditions.
These alterations suggest a shift in cardiac mechanotransduction pathways, potentially impacting cardiovascular health in altered gravity environments.

Abstract

Although hypergravity may influence cardiac mechanosensitivity, the effects on specific ion channels remain inadequately understood. This research examined the effects of long-term hypergravity on the functional activity and transcriptional expression of mechanosensitive channels (MSCs) in rat ventricular cardiomyocytes. After 14 days of exposure to 4g, rats were subjected to molecular and electrophysiological analyses. Significant remodeling of MSC-encoding genes was revealed by RNA-seq. Trpm7 (+41.23%, p = 0.0073) and Trpc1 (+68.23%, p = 0.0026) were significantly upregulated among non-selective cation channels, while Trpv2 (−62.19%, p = 0.0044) and Piezo2 (−57.58%, p = 0.0079) were significantly downregulated. Kcnmb1 (−47.84%, p = 0.0203) was suppressed, whereas Traak/K2P4.1 showed a strong increase (+239.48%, p = 0.0092), among K+-selective MSCs. Furthermore, Kir6.1 was significantly downregulated (−75.8%, p = 0.0085), whereas Kir6.2 was significantly upregulated (+38.58%, p = 0.0317). These results suggest targeted transcriptional reprogramming that suppresses pathways associated with maladaptive Ca2+ influx while enhancing Ca2+-permeable mechanosensitive channels alongside stabilized K+ conductance. At the structural level, cardiomyocytes from hypergravity exposure showed a 44% increase in membrane capacitance, consistent with hypertrophic remodeling, and sarcomere elongation (p < 0.001). Functionally, stretch-activated current (ISAC) was markedly hypersensitive in patch-clamp analysis: currents were induced at very small displacements (1–2 µm) and were significantly larger under 4–10 µm stretch (222–107% of control values). These findings indicate that chronic hypergravity induces coordinated molecular, structural, and functional remodeling of cardiomyocytes, characterized by increased membrane excitability, compensatory stabilizing mechanisms, and enhanced Ca2+ signaling. This demonstrates the flexibility of cardiac mechanotransduction under prolonged gravitational stress, with potential implications for understanding cardiovascular risks, arrhythmias, and hypertrophy associated with altered gravity environments.

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