title: Neurotensin increases the cationic conductance of rat substantia nigra dopaminergic neurons through the inositol 1,4,5-trisphosphate-calcium pathway.
abstract: Whole-cell patch-clamp recordings were used to investigate electrophysiological effects of neurotensin on acutely isolated dopaminergic (DA) neurons of the rat substantia nigra pars compacta (SNC). During current-clamp recordings, neurotensin depolarized DA neurons and triggered action potentials. Under voltage-clamp recordings, neurotensin evoked an inward current at a holding potential of -50 mV. Neurotensin-induced inward currents reversed the direction at -5 mV and became smaller as the membrane potential was hyperpolarized from -75 mV. With potassium-free recording solutions, neurotensin evoked voltage-insensitive cationic currents. With sodium-free external solution, neurotensin also caused inward currents by reducing the inwardly rectifying potassium conductance. Neurotensin-induced inward currents mainly resulted from an increase in a non-selective cationic conductance. Neurotensin-evoked cationic currents were inhibited by the intracellular perfusion of 1 mM guanosine-5'-O-(2-thiodiphosphate). In DA neurons internally perfused with 0.5 mM guanosine-5'-O-(3-thiotriphosphate), the cationic current produced by neurotensin became irreversible. Pretreating DA neurons with 500 ng/ml pertussis toxin (PTX) did not significantly affect the ability of neurotensin to evoke cationic currents. Internal perfusion of heparin (2 mg/ml), an inositol 1,4,5-trisphosphate (IP3) receptor antagonist, and buffering intracellular calcium with the Ca(2+)-chelator BAPTA (10 mM) suppressed neurotensin-induced cationic currents. Dialyzing DA neurons with protein kinase C (PKC) inhibitors, staurosporine and PKC(19-31), failed to prevent neurotensin from evoking cationic currents. It is concluded that PTX-insensitive G-proteins mediate neurotensin-induced enhancement of the cationic conductance of SNC DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Neurology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, ROC.
authors.forename: T
authors.initials: T
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: H L
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002412:Cations / Q000378:metabolism; D004298:Dopamine / Q000502:physiology; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007473:Ion Channels / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D009496:Neurotensin / Q000502:physiology*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D002412:Cations; D007473:Ion Channels; D010566:Virulence Factors, Bordetella; D009496:Neurotensin; D015544:Inositol 1,4,5-Trisphosphate; D037342:Pertussis Toxin; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D011188:Potassium; D002118:Calcium; D004298:Dopamine