Intracellular calcium signaling machinery in vascular smooth muscle (VSMC Ca2+ signaling)

The intracellular calcium signaling machinery in vascular smooth muscle cells (VSMCs) is a complex, integrated system of proteins that regulates cytosolic calcium levels to control vascular tone and structural remodeling (Berridge, 2008, J Physiol). Key components include L-type voltage-gated calcium channels (VGCCs) for extracellular influx, and inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) for calcium release from the sarcoplasmic reticulum (Kuo and Ehrlich, 2015, J Gen Physiol). This machinery facilitates excitation-contraction coupling, where an increase in intracellular calcium triggers myosin light chain kinase (MLCK) activation, leading to muscle contraction (StatPearls, 2023). Beyond contraction, calcium signaling also drives VSMC proliferation and migration, which are critical in vascular repair and the progression of atherosclerosis (Touyz et al., 2018, Cardiovasc Res). Dysregulation of these pathways, such as overactive calcium influx or impaired SERCA-mediated sequestration, is a primary driver of hypertension and pulmonary arterial hypertension (PubMed, 2021). Pharmacological targeting of this machinery is a cornerstone of cardiovascular medicine, primarily through calcium channel blockers like amlodipine that inhibit VGCCs to induce vasodilation (PubChem, 2024). Emerging therapeutic strategies focus on more specific components like store-operated calcium entry (SOCE) via STIM1 and Orai1 to treat proliferative vascular disorders (Nature Reviews Cardiology, 2020).

Other names

Vascular smooth muscle calcium signaling pathwayVSMC excitation-contraction coupling machineryVascular smooth muscle Ca2+ handling system

Inhibition of L-type voltage-gated calcium channels; Inhibition of sarcoplasmic reticulum calcium release; Activation of calcium-sequestration pumps (SERCA); Modulation of store-operated calcium entry (SOCE); Enhancement of cyclic nucleotide-mediated calcium desensitization.