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Proposed mechanism of Tat-induced NMDAR potentiation and adaptation. Tat interacts with LRP leading to the activation Src-kinase. Src kinase potentiates NMDA-evoked [Ca2+]i responses. Increased Ca2+ flux activates NOS to produce NO. NO binds to sGC stimulating the synthesis of cGMP. cGMP then activates PKG leading to the reduction of NMDA-evoked [Ca2+]I responses. Solid and dashed arrows represent direct and potentially indirect connections, respectively.
