Figure 6.

IRAG knockdown impairs NO-mediated vasodilation. (A) Summary data showing no significant difference in the constriction response to elevated levels of extracellular KCl (60 mM) between cerebral arteries transfected with control morpholinos and those transfected with IRAG-targeted morpholinos (n = 9 arteries from three animals). (B) Summary data showing no difference in the myogenic tone of cerebral arteries between those transfected with control morpholinos and those transfected with IRAG-targeted morpholinos (n = 3 arteries from three animals). (C) Representative traces showing concentration-dependent dilation of cerebral arteries transfected with control or IRAG-targeted morpholinos in response to SNAP. (D) SNAP concentration-response curve (100 nM–100 µM) for dilation of cerebral arteries transfected with control or IRAG-targeted morpholinos. The EC₅₀ for control arteries was 0.2 µM and that for IRAG KD was 1.3 µM (n = 6 arteries from four animals in each group). (E) Proposed mechanism of NO-induced inhibition of TRPM4. NO, nitric oxide; sGC, soluble guanylyl cyclase; GTP, guanosine triphosphate; cGMP, cyclic guanosine monophosphate; PKG, cGMP-dependent protein kinase; IP₃R, inositol 1,4,5-triphosphate receptor; IRAG, IP₃R-associated cGMP-kinase substrate; SR, sarcoplasmic reticulum; and TRPM4, transient receptor potential melastatin 4.