Chronic depolarization induced by veratridine increases the survival of rat retinal ganglion cells 'in vitro'
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 Ca(2+) channels), 25 µM benzamil (an inhibitor of Na(+) channels), 30 µM dantrolene and 7.5 µM caffeine (both inhibitors of Ca(2+) release from the endoplasmatic reticulum) and 10 µM BAPTA-AM (an intracellular Ca(2+) chelator). However, 5 µM nifedipine (a selective inhibitor of voltage-dependent L-type Ca(2+) 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 Ca(2+) release, activation of tyrosine kinase enzymes and cellular proliferation. They also indicate that cholinergic activity plays an important role in the veratridine effect.
Fernandes Pereira SP
Departamento de Neurobiologia, Instituto de Biologia, Universidade Federal Fluminense, Caixa Postal 100180, 24001-970, Niterói, RJ, Brazil
Giestal de Araujo E