Calcium ion (Ca²⁺), as a crucial second messenger in plant cells, plays a central role in sensing and responding to heavy metal stress. This review systematically summarizes recent advances in the dual regulatory mechanisms of Ca²⁺signaling for the uptake and tolerance of heavy metals such as cadmium and lead. On the one hand, heavy metals can trigger specific Ca²⁺ signatures-transient elevations or characteristic oscillations—through three pathways: direct activation of Ca²⁺ channels, indirect induction of reactive oxygen species (ROS)bursts, and disruption of Ca²⁺ homeostasis. On the other hand, these spatiotemporally distinct Ca²⁺ signals are decoded by sensors including calmodulin, calcium-dependent protein kinases, and calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) complexes, which then precisely regulate the expression and activity of heavy metal transporters, such as CNGCs and NRAMPs, through transcriptional and post-translational modifications. This enables a dual regulatory mode-suppressing uptake, promoting efflux, or vacuolar sequestration-while concurrently activating antioxidant and chelation-based detoxification pathways to maintain ion homeostasis and redox balance. Furthermore, arbuscular mycorrhizal fungi symbiosis can synergistically modulate plant metal uptake and tolerance by reshaping the spatiotemporal patterns of host Ca²⁺ signals, altering ion transport profiles, and enhancing detoxification pathways. In conclusion, this review emphasizes that the Ca²⁺ pathway-centered “perception-decoding-execution” network is key to regulating heavy metal uptake in plants. Future research should focus on identifying metal-specific Ca²⁺ fingerprints, functionally validating key channels and decoding modules, and developing applications combined with rhizosphere microbial interventions, thereby providing theoretical and technical support for low-heavy-metal-accumulation cultivation of medicinal plants and crops, as well as for soil remediation.

Ca²⁺ signaling  /  calcium channels  /  calcium-dependent protein kinases  /  calcineurin B-like protein-CBL-interacting protein kinase complexes  /  heavy metal uptake  /  arbuscular mycorrhizal fungi  /  environmental stress