Role of inositol 1,4,5-trisphosphate receptors in vascular smooth muscle
This study has examined the expression and distribution of the type-1, type-2 and type-3 InsP3R subtypes in vascular smooth muscle in order to establish the roles of these subtypes. Immunoblotting of portal vein and aorta from neonatal (2-5 day old) and developed (6 week old) rat revealed comparatively greater expression of type-2 and type-3 InsP3R in the neonatal rat, compared to developed, and expression of type-1 InsP3R was decreased in neonatal rat compared to developed. In addition, there was a reorganisation of the internal calcium stores and altered intracellular InsP3R distribution observed between neonatal and developed rat. In permeabilised portal vein from developed rat, application of 100μM InsP3 induced contractions of 54±7% of maximal activated contraction, whereas the permeabilised portal vein from neonatal rat, InsP3 failed to induce contractility, indicating the type-1 InsP3R, but not type-2 and type-3 InsP3R subtypes are involved in excitation-contraction coupling. InsP3R subtype expression was also investigated in primary cultures of developed aortic cells. When seeded at subconfluent density these cells modulate to a "synthetic" phenotype believed to be similar to that found in vascular injury. InsP3R subtype expression is regulated during cell differentiation, and also in some vascular disease states. The type-2 and type-3 InsP3R subtypes may be involved in proliferating vascular smooth muscle, whereas the role of the type-1 InsP3R subtype is in excitation-contraction coupling in developed VSM. Therefore InsP3R expression may be a means of regulating the phenotypic properties of the vascular smooth muscle cell in vivo.