title: Neurotensin effects on N-type calcium currents among rat pallidal neurons: an electrophysiological and immunohistochemical study.
abstract: The tridecapeptide neurotensin (NT) is involved in the modulation of dopamine (DA)-mediated functions in the nigrostriatal and mesocorticolimbic pathways. Its relevance in mammalian globus pallidus (GP) is questioned. A recent electrophysiological study on GP slices described NT-mediated robust membrane depolarization, depending upon the suppression of potassium conductance and/or the activation of cation current. Here, we have studied whether NT also affected high-voltage-activated calcium (Ca(2+)) currents, by means of whole-cell recordings on isolated GP neurons. In our hands, the full peptide and the segment NT8-13 reversibly inhibited N-like Ca(2+) current in about 60% of the recorded dissociated neurons, irrespective of their capacitance. The NT-mediated modulation showed no desensitization and was antagonized by the NT1 antagonists SR48692 and SR142948. These results imply an abundant expression of NTS(1) on GP cell somata. Then, we performed a light and immunofluorescence-confocal microscopy study of NTS(1) localization among GP neurons. We found that NTS(1) is localized in about 56% of GP neurons in both subpopulations of neurons, namely parvalbumin positive and negative. We conclude that NT, likely released from the striatal terminals in GP, acts through the postsynaptic NTS(1) preferentially localized in the lateral aspects of the GP. These data suggest a new implication (neither merely presynaptic nor simply "excitatory") for NT in the modulation of GP firing pattern. In addition, NT might have a role in affecting the interplay among the endogenous release of GABA/glutamate and DA. This hypothesis might have implications on both sensori-motor and associative functions of the GP and should be tested in DA-denervated disease models.
authors.affiliation: Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Martella
authors.forename: Vincenza
authors.initials: V
authors.lastname: D'Angelo
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Fusco
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadoni
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology; D009924:Organ Culture Techniques; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D020864:Calcium Channels, N-Type; D010320:Parvalbumins; D010446:Peptide Fragments; D018028:Receptors, Neurotensin; D009496:Neurotensin; D005680:gamma-Aminobutyric Acid; D004298:Dopamine