SOMATOSTATIN-14 AND SOMATOSTATIN-28 INHIBIT CALCIUM CURRENTS IN RAT NEOCORTICAL NEURONS

The prosomatostatin-derived peptides, somatostatin-14 and somatostatin-28, are believed to function as neurotransmitters or neuromodulators in the cerebral cortex. To investigate the molecular mechanisms by which these peptides induce their physiological effects in the cerebral cortex, we have examined the effects of somatostatin-14 and somatostatin-28 on voltage-dependent Ca2+ currents in rat neocortical neurons in culture. Ca2+ currents were recorded using whole-cell patch-clamp techniques under conditions in which K+ and Na+ currents were blocked. Ca2+ currents were induced by depolarization from the holding potential of -80 mV. Somatostatin-14 (100 nM) and somatostatin-28 (100 nM) did not significantly affect low-voltage activated Ca2+ currents, but blocked high-voltage activated Ca2+ currents and slowed the activation of this current. The effects of both peptides were concentration-dependent and reversible. Furthermore, the effects of somatostatin-14 and somatostatin-28 on the high-voltage activated Ca2+ currents were not additive, suggesting that both peptides regulate this ionic current through similar cellular mechanisms. When patch pipettes used to record the Ca2+ currents contained 100 μ M cAMP and 0.5 mM isobutylmethylxanthine, a phosphodiesterase inhibitor, somatostatin-14 and somatostatin-28 still inhibited Ca2+ currents, indicating that the effects of these peptides on the Ca2+ currents were cAMP-independent. Inclusion of the non-hydrolysable guanine triphosphate analogue, guanine triphos-phate-gamma-thiol (500 μM) in the recording electrode produced effects similar to those induced by somatostatin-14 or somatostatin-28, suggesting the involvement of guanine nucleotide binding proteins in the actions of the peptides on the Ca2+ currents. This hypothesis is supported by the finding that pretreatment of the neurons with pertussis toxin greatly reduced the abilities of somatostatin-14 and somatostatin-28 to inhibit Ca2+ currents. Our results suggest that somatostatin-14 and somatostatin-28 inhibit Ca2+ currents of rat neocortical neurons through a cAMP-independent mechanism involving pertussis toxin-sensitive guanine nucleotide binding proteins. © 1990.