Dr. Chen, Chien-Chang
Research Fellow
- 02-2652-3944 (Lab) (Room No: N713)
- 02-2652-3522 (Office)
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Specialty:
- Chronic Pain
- Calcium Channel
- Cardiovascular Disease
Education and Positions:
Ph.D., University of Illinois, Urbana-Champaign
Highlight Detail
Cav3.2 T-type calcium channel regulates mouse platelet activation and arterial thrombosis
Dr. Chen, Chien-Chang
Journal of thrombosis and haemostasis, Jul 01, 2022
Background
Cav3.2 is a T-type calcium channel that causes low-threshold exocytosis. T-type calcium channel blockers reduce platelet granule exocytosis and aggregation. However, studies of the T-type calcium channel in platelets are lacking.
Objective
To examine the expression and role of Cav3.2 in platelet function.
Methods
Global Cav3.2−/− and platelet-specific Cav3.2−/− mice and littermate controls were used for this study. Western blot analysis was used to detect the presence of Cav3.2 and activation of the calcium-responsive protein extracellular signal-regulated kinase (ERK). Fura-2 dye was used to assess platelet calcium. Flow cytometry and light transmission aggregometry were used to evaluate platelet activation markers and aggregation, respectively. FeCl3-induced thrombosis and a microfluidic flow device were used to assess in vivo and ex vivo thrombosis, respectively.
Results
Cav3.2 was expressed in mouse platelets. As compared with wild-type controls, Cav3.2−/− mouse platelets showed reduced calcium influx. Similarly, treatment with the T-type calcium channel inhibitor Ni2+ decreased the calcium influx in wild-type platelets. As compared with controls, both Cav3.2−/− and Ni2+-treated wild-type platelets showed reduced activation of ERK. ATP release, P-selectin exposure, and αIIbβ3 activation were reduced in Cav3.2−/− and Ni2+-treated wild-type platelets, as was platelet aggregation. On in vivo and ex vivo thrombosis assay, Cav3.2 deletion caused delayed thrombus formation. However, tail bleeding assay showed intact hemostasis.
Conclusion
These results suggest that Cav3.2 is required for the optimal activation of platelets.