NITRIC-OXIDE REDUCES DEPOLARIZATION-INDUCED CALCIUM INFLUX IN PC12 CELLS BY A CYCLIC GMP-MEDIATED MECHANISM

The present study was undertaken to determine whether nitric oxide (NO ) alters voltage-dependent changes in intracellular calcium levels ([C a2+](i)) using PC12 cells as a neuronal model. The addition to PC12 ce lls of sodium nitroprusside (SNP), which spontaneously releases NO in aqueous solution, significantly inhibited the KCl-stimulated increase in [Ca2+](i). The inhibitory action of SNP was concentration-dependent and was mimicked by hydroxylamine which also generates NO. Both L-typ e (nifedipine sensitive) and N-type (omega-conotoxin sensitive) voltag e-dependent Ca2+ channels are present in PC12 cells and may be affecte d by NO-generating agents. In contrast, SNP did not alter [Ca2+](i) in response to purinergic receptor stimulation. Preincubation of PC12 ce lls with 8-bromo-cyclic GMP also inhibited the KCl-stimulated increase in [Ca2+](i). In addition, inclusion of the guanylyl cyclase inhibito r, LY83583, blocked the inhibitory action of SNP on the voltage-sensit ive changes in [Ca2+](i). The results suggest that NO selectively inhi bits voltage-dependent calcium influx in neuronal cells through a cycl ic GMP-dependent mechanism.