Implications of purinergic receptor-mediated intracellular calcium transients in neural differentiation

Purinergic receptors participate, in almost every cell type, in controlling metabolic activities and many physiological functions including signal transmission, proliferation and differentiation. While most of P2Y receptors induce transient elevations of intracellular calcium concentration by activation of intracellular calcium pools and forward these signals as waves which can also be transmitted into neighboring cells, P2X receptors produce calcium spikes which also include activation of voltage-operating calcium channels. P2Y and P2X receptors induce calcium transients that activate transcription factors responsible for the progress of differentiation through mediators including calmodulin and calcineurin. Expression of P2X2 as well as of P2X7 receptors increases in differentiating neurons and glial cells, respectively. Gene expression silencing assays indicate that these receptors are important for the progress of differentiation and neuronal or glial fate determination. Metabotropic receptors, mostly P2Y1 and P2Y2 subtypes, act on embryonic cells or cells at the neural progenitor stage by inducing proliferation as well as by regulation of neural differentiation through NFAT translocation. The scope of this review is to discuss the roles of purinergic receptor-induced calcium spike and wave activity and its codification in neurodevelopmental and neurodifferentiation processes.

H.U. acknowledges grant support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Project No. 2006/61285-9 and 2012/50880-4, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and the Provost´s Office for Research of the University of São Paulo (Programa de Incentivo à Pesquisa, Project No. 2011.1.9333.1.3, NAPNA-USP), Brazil. R.R.R. is grateful for grant support by CNPq-MCT and Instituto Nacional de Ciência e Tecnologia de Nanomateriais de Carbono, CNPq and Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil. T.G.’s doctoral thesis is supported by a fellowship from FAPESP.