Role of TRPC3 Channel in Human Internal Mammary Artery

Abstract

Background and Aims. Intracellular calcium regulation in endothelial cells depends on transient receptor potential channels (TRPs). Canonical TRPs (TRPCs) are now recognized as the most important Ca2+-permeable cation channels in vascular endothelium and TRPC3 channel is reported to play a role in vasodilation in animal vessels. However, little is known about the role of TRPCs in human arteries. We therefore tested the hypothesis that TRPCs play a role in human arteries. Methods. Cumulative concentration-relaxation curves to acetylcholine (-11 to -4.5 log M) were established in the human internal mammary artery (IMA) rings (n = 42) taken from 28 patients undergoing coronary artery bypass grafting in precontraction induced by U46619 (-8 log M) in the absence or presence of SKF96365 (10 mu mol/L) or Pyr3 (3 mu mol/L). Protein expressions of TRPC3 were determined by Western blot and immunohistochemistry staining. Results. The maximal relaxation induced by acetylcholine was significantly attenuated by the nonspecific cation channels inhibitor, SKF96365 (48.2 +/- 3.7 vs. 66.0 +/- 0.9% in control, p lt 0.01) or the selective TRPC3 blocker, Pyr3 (58.4 +/- 2.3% vs. 67.7 +/- 1.1% in control, p lt 0.01). Protein expression of TRPC3 was detected in human 1MA. Conclusions. TRPC3 exists and plays a role in the acetylcholine-induced endothelium-dependent relaxation in the human IMA. This study suggests that TRPC3 may be a potential new target in endothelial protection in patients with endothelial dysfunction such as in patients with coronary artery disease in order to improve the long-term patency of the grafting vessels.