Galanin inhibits continuous and phasic firing in rat hypothalamic magnocellular neurosecretory cells

The effects of galanin (GAL) on magnocellular neurosecretory cells (MNCs) were examined during microelectrode recordings from supraoptic neurons in superfused hypothalamic explants. Application of the full-length peptide (GAL1-29) or of the N-terminal fragment GAL1-16 produced reversible membrane hyperpolarization with an IC50 near 10 nM. These effects were associated with an increase of membrane conductance, with a reversal potential near -70 mV, and were not blocked by tetrodotoxin, indicating that the receptors mediating these effects are located postsynaptically. Hyperpolarizing responses were also observed in response to the GAL-like chimeric ligands M35 and M40, suggesting that these behave as partial agonists at galanin receptors. The reversal potential of the GAL-mediated effect was unaffected by reducing extracellular chloride or by intracellular chloride injection, indicating that the effects of galanin are not mediated by modulation of chloride conductances. In contrast, reducing the external concentration of potassium ions from 3 to 1 mM shifted the reversal potential of the responses to -85 mV, suggesting the involvement of a potassium conductance. When tested on spontaneously active MNCs, the hyperpolarizing effects of galanin were associated with a suppression of firing in both continuously active and phasically active neurons. Inhibition of phasic bursts was mediated both through the inhibitory effects of the hyperpolarization and through a GAL-mediated inhibition of the depolarizing afterpotential that is responsible for the production of individual bursts. These results suggest that galanin may be a potent endogenous modulator of firing pattern in hypothalamic neuroendocrine cells.