Objectives: 

Vascular smooth muscle contracts in response to an increase in intracellular Ca2+ that depends on Ca2+ release from sarcoplasmic reticulum (SR) and Ca2+ entry through voltage dependent and voltage independent ion channels. Voltage-dependent CaV1.2 L-type Ca2+ channels (LTCC) are considered the main route for calcium entry in vascular smooth muscle cells (VSMC). However, it is now agreed that store-operated Ca2+ channels (SOCC) play an important role in vascular tone regulation. The aim of this study was to characterize the communication between SOCC and LTCC and their role in the agonist-induced vasoconstriction.

Materials: 

We have used wild type and smooth muscle-selective conditional CaV1.2 knockout mice to study arterial rings contractility as well as intracellular Ca2+ mobilization and membrane potential in isolated smooth muscle cells.

Results: 

We have found that agonist as serotonin induced aorta vasoconstriction was sensitive to LTCC and SOCC inhibitors indicating the participation of both conductance in vessels contraction. Moreover, vasoconstriction induced by agonist or by thapsigargin, which selectively activate SOCC, was significantly attenuated in arterial rings from CaV1.2 knockout mice compared to wild type. In isolated VSMC, thapsigargin evoked a prominent cytosolic Ca2+ increase that was sensitive to nifedipine, demonstrating that SOCC activation promotes LTCC opening. Furthermore, in current clamp configuration, thapsigargin induced depolarization in wild type VSMC which was significantly lower in CaV1.2 knock-out VSMC, confirming that SOCC activated pathway involves a depolarization and further LTCC opening.

Conclusions: 

These data suggest a functional interaction and co-activation of SOCC and LTCC in VSMC. LTCC activation during agonist-induced vasoconstriction seems triggered by store-operated Ca2+ entry through SOCC.