Canonical Transient Receptor Potential 1 Plays a Role in Basic Fibroblast Growth Factor (bFGF)/FGF Receptor-1-Induced Ca super(2)+ Entry and Embryonic Rat Neural Stem Cell Proliferation

• Published in: The Journal of neuroscience 2005-03, Vol.25 (10), p.2687-2701
• Main Authors: Pla, Alessandra Fiorio, Maric, Dragan, Brazer, So-Ching, Giacobini, Paolo, Liu, Xibao, Chang, Yoong Hee, Ambudkar, Indu S, Barker, Jeffery L
• Format: Article
• Language: English
• ISSN: 0270-6474

Basic fibroblast growth factor (bFGF) and its major receptor FGF receptor-1 (FGFR-1) play an important role in the development of the cortex. The mechanisms underlying the mitogenic role of bFGF/FGFR-1 signaling have not been elucidated. Intracellular Ca super(2+) concentrations ([Ca super(2+)] sub(i)) in proliferating cortical neuroepithelial cells are markedly dependent on Ca super(2+) entry (Maric et al., 2000a). The absence of voltage-dependent Ca super(2+) entry channels, which emerge later, indicates that other membrane mechanisms regulate [Ca super(2+)] sub(i) during proliferation. Canonical transient receptor potential (TRPC) family channels are candidates because they are voltage independent and are expressed during CNS development (StrUbing et al., 2003). Here, we investigated the involvement of TRPC1 in bFGF-mediated Ca super(2+) entry and proliferation of embryonic rat neural stem cells (NSCs). Both TRPC1 and FGFR-1 are expressed in the embryonic rat telencephalon and coimmunoprecipitate. Quantitative fluorescence-activated cell sorting analyses of phenotyped telencephalic dissociates show that [approx]80% of NSCs are TRPC1 super(+), proliferating, and express FGFR-1. Like NSCs profiled ex vivo, NSC-derived progeny proliferating in vitro coexpress TRPC1 and FGFR1. Antisense knock-down of TRPC1 significantly decreases bFGF-mediated proliferation of NSC progeny, reduces the Ca super(2+) entry component of the Ca sub(i) super(2+) response to bFGF without affecting Ca super(2+) release from intracellular stores or 1-oleoyl-2-acetyl-sn-glycerol-induced Ca super(2+) entry, and significantly blocks an inward cation current evoked by bFGF in proliferating NSCs. Both Ca super(2+) influx evoked by bFGF and NSC proliferation are attenuated by Gd super(3+) and SKF96365 two antagonists of agonist-stimulated Ca super(2+) entry. Together, these results show that TRPC1 contributes to bFGF/FGFR-1-induced Ca super(2+) influx, which is involved in self-renewal of embryonic rat NSCs.