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

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. <i>Trpm7</i> (+41.23%, <i>p</i> = 0.0073) and <i>Trpc1</i> (+68.23%, <i>p</i> = 0.0026) were significantly upregulated among non-selective cation channels, while <i>Trpv2</i> (-62.19%, <i>p</i> = 0.0044) and <i>Piezo2</i> (-57.58%, <i>p</i> = 0.0079) were significantly downregulated. <i>Kcnmb1</i> (-47.84%, <i>p</i> = 0.0203) was suppressed, whereas <i>Traak</i>/K2P4.1 showed a strong increase (+239.48%, <i>p</i> = 0.0092), among K⁺-selective MSCs. Furthermore, <i>Kir6.1</i> was significantly downregulated (-75.8%, <i>p</i> = 0.0085), whereas <i>Kir6.2</i> was significantly upregulated (+38.58%, <i>p</i> = 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 (<i>p</i> < 0.001). Functionally, stretch-activated current (<i>I</i>_SAC) 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.