Somatostatin modulates Ca2+ currents in neostriatal neurons.

摘要

Somatostatin is synthesized and released by aspiny interneurons of the neostriatum. This work investigates the actions of somatostatin on rat neostriatal neurons of medium size (ca. 6 pF). Somatostatin (1 microM) reduces both calcium action potentials (20 mM tetraethylammonium) by ca. 24% and calcium currents by ca. 35%, in all cells tested. This action was produced in the presence of tetrodotoxin and in dissociated cells and was blocked by cyclo(-7-aminoheptanoyl-phe-d-try-lys-O-benzyl-thr) acetate (CPP-1), a somatostatin receptor antagonist. Except for nitrendipine (5 microM), several calcium channel antagonists, 1 microM omega-conotoxin GVIA, 400 nM omega-agatoxin TK, and 1 microM omega-conotoxin MVIIC, partially occluded somatostatin action. According to the calcium channel types known to be blocked by these antagonists, P/Q-type channels appeared to be the channels mainly modulated by somatostatin, followed by N-type channels. Since these channel types generate the afterhyperpolarizing potential in spiny neurons, we investigated the action of somatostatin on this event. Somatostatin reduces the amplitude of the afterhyperpolarizing potential by ca. 39%. This action is occluded by omega-agatoxin TK and omega-conotoxin MVIIC but not by omega-conotoxin GVIA or nicardipine. Thus, the action of somatostatin on the afterhyperpolarizing potential is mainly mediated by P/Q-type calcium channels. The block of the slow afterhyperpolarizing potential made most neurons exhibit an irregular firing mode, suggesting that ion currents other than calcium may also be affected by somatostatin.We conclude that somatostatin exerts a direct postsynaptic effect on neostriatal neurons via the activation of somatostatin receptors. This action affects non-L-type calcium channels and therefore modifies the afterhyperpolarizing potential and the firing pattern. It is proposed that somatostatin and its analogues may have profound effects on the motor functions controlled by the basal ganglia.