Effects of neurotensin on rat supraoptic nucleus neurones in vitro

1. The electrophysiological actions of neurotensin on magnocellular neurosecretory cells (MNCs) were examined during intracellular recording from seventy-three supraoptic nucleus neurones in superfused explants of rat hypothalamus. 2. Application of neurotensin tridecapeptide (NT(1-13); 1 nM to 3 microM) caused a membrane depolarization and reversibly attenuated the after-hyperpolarization (AHP) which followed current-evoked spike trains. This effect was accompanied by increased firing frequency during depolarizing current pulses evoked from a fixed potential. 3. The effects of neurotensin could be mimicked by the C-terminal fragment, NT(8-13), but not by the N-terminal fragment, NT(1-8). 4. Depolarizing responses to NT(1-13) or NT(8-13), retained during K+ channel blockade with internal Cs+, were accompanied by increased membrane conductance. Current- and voltage-clamp analyses revealed that neurotensin-evoked depolarizations result partly from the activation of a non-selective cationic conductance reversing near -34 mV. 5. Depolarizing responses to neurotensin were retained in the presence of TTX or in Ca(2+)-free solutions, indicating the involvement of receptors located on the plasma membrane of MNCs themselves. 6. Through these effects endogenously released neurotensin may modulate excitability, activity patterns and secretion from the hypothalamo-neurohypophysial axis.