Predominant role of type 1 IP3 receptor in aortic vascular muscle contraction

Inositol 1,4,5-trisphosphate receptor (IP3R) plays a crucial role in generating Ca2+ signaling and three subtypes of IP3R have been identified. In spite of a high degree of similarity among these subtypes, their effects on spatio-temporal Ca2+ patterns are specific and diverse; therefore the physiological significance of the differential expression levels of IP3R subtypes in various tissues remains unknown. Here, we examined the relative contribution of the specific subtype of IP3Rs to the agonist-induced Ca2+ signaling and contraction in IP3R-deficient vascular smooth muscle cells and found that IP3R1 deficient cells exclusively showed less sensitivity to the agonist, compared to those from the other genotypes. We also found that IP3R1 dominantly expressed in vascular aortae on a consistent basis, and that phenylephrine (PE)-induced aortic muscle contraction was reduced specifically in IP3R1-deficient aortae. Taken together, we concluded that IP3R1 plays a predominant role in the function of the vascular smooth muscle in vivo.