Neurotensin (3-13 μM) depolarized the membrane and increased the firing discharge of dopaminergic cells in slices of the rat mesencephalon. Under voltage-clamp, at holding potentials from -50 to -60 mV (near the resting membrane potential), neurotensin produced a sustained inward shift in the holding current. This inward current was reduced with the hyperpolarization of the membrane to -125 mV. It was resistant to tetrodotoxin, but it was diminished following the perfusion with low sodium (choline chloride substitution) solution. It persisted in low calcium (1-5 mM). Changes in the intracellular concentration of chloride did not affect neurotensin-induced current. The neurotensin-induced inward current did not reverse at hyperpolarized potentials in 10.5 mM extracellular K+. It was also seen in the presence of the potassium channel blockers tetraethylammonium (10-20 mM), barium (1 mM), apamine (1 μM) and 4-aminopyridine (1-5 mM). Also the extracellular application of cesium (1-5 mM) had no effect on the cellular responsiveness to neurotensin. The action of neurotensin appears to be mediated, at least partially, by a TTX-insensitive but voltage-dependent inward current carried by sodium. The non-dopaminergic cells of the substantia nigra and ventral tegmental area were not affected by neurotensin.
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