Affiliation: | a Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Caixa Postal 100180, 24001-970, Niterói, RJ, Brazil b Departamento de Farmacologia Básica e Clínica Experimental and Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, 21949-900, Rio de Janeiro, RJ, Brazil |
Abstract: | During the last decades it has been shown that trophic molecules released by target, afferent and glial cells play a pivotal role controlling neuronal cell death. Trophic molecules are able to inhibit this regressive event during development as well as during degenerative diseases. One of the mechanisms involved in the control of neuronal survival by afferent cells requires the release of trophic molecules stimulated by electrical activity. It has been demonstrated that veratridine (a depolarizing agent that keeps the Na+ channels opened) induces an increase in neuronal survival. In the present work we show that 3 μM veratridine induced a two-fold increase on the survival of retinal ganglion cells after 48 h in culture. The veratridine effect was inhibited by 50 μM amiloride (an inhibitor of Ca2+ channels), 25 μM benzamil (an inhibitor of Na+ channels), 30 μM dantrolene and 7.5 μM caffeine (both inhibitors of Ca2+ release from the endoplasmatic reticulum) and 10 μM BAPTA-AM (an intracellular Ca2+ chelator). However, 5 μM nifedipine (a selective inhibitor of voltage-dependent -type Ca2+ channels) and 100 μM MK 801 (an inhibitor of NMDA receptors) did not block the veratridine effect. On the other hand, treatment with 10 μM genistein (an inhibitor of tyrosine kinase enzymes), 20 μM fluorodeoxyuridine (an inhibitor of cell proliferation) or 10 μM atropine (an antagonist of muscarinic receptors) completely abolished the effect of veratridine. Taken together, our results indicate that veratridine increases the survival of rat retinal ganglion cells through mechanisms involving Na+ influx, intracellular Ca2+ release, activation of tyrosine kinase enzymes and cellular proliferation. They also indicate that cholinergic activity plays an important role in the veratridine effect. |