Neurotensin and Substance P Inhibit Low- and High-Voltage-Activated Ca2+ Channels in Cultured Newborn Rat Nucleus Basalis Neurons

• Published in: Journal of neurophysiology 1997-09, Vol.78 (3), p.1341-1352
• Main Authors: Margeta-Mitrovic, Marta, Grigg, John J, Koyano, Konomi, Nakajima, Yasuko, Nakajima, Shigehiro
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Basal Ganglia - cytology; Basal Ganglia - drug effects; Basal Ganglia - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Calcium Channels - metabolism; Cells, Cultured; Electrophysiology; GTP-Binding Proteins - metabolism; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Neurons - drug effects; Neurons - metabolism; Neurotensin - pharmacology; Patch-Clamp Techniques; Pertussis Toxin; Rats; Substance P - pharmacology; Virulence Factors, Bordetella - pharmacology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.1997.78.3.1341

Marta Margeta-Mitrovic , John J. Grigg , Konomi Koyano , Yasuko Nakajima , and Shigehiro Nakajima Departments of Pharmacology and Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612 Margeta-Mitrovic, Marta, John J. Grigg, Konomi Koyano, Yasuko Nakajima, and Shigehiro Nakajima. Neurotensin and substance P inhibit low- and high-voltage-activated Ca 2+ channels in cultured newborn rat nucleus basalis neurons. J. Neurophysiol. 78: 1341-1352, 1997. Inhibition of Ca 2+ currents by the excitatory neurotransmitters neurotensin and substance P was investigated in cultured nucleus basalis neurons with the use of the whole cell patch-clamp technique. The whole cell Ca 2+ current, elicited from a holding potential of 80 mV by a step pulse to 0 mV and measured at 100 ms, was inhibited 67.9% by neurotensin and 57.6% by substance P. Low-voltage-activated (LVA) Ca 2+ current, elicited by a step pulse to 40 mV from a holding potential of 90 mV, was inhibited by both neurotensin (26.2%) and substance P (24.1%). High-voltage-activated Ca 2+ currents were separated with the use of the Ca 2+ channel antagonists. Nimodipine (3 µM) inhibited 24.2% of the whole cell Ca 2+ current elicited by a step to 0 or +10 mV and measured at 100 ms. Under the same conditions, -conotoxin ( -CgTx)-GVIA (0.5 µM) inhibited 46.4%, -CgTx-GVIA + nimodipine 58.7%, and -CgTx-MVIIC (5 µM) + nimodipine 75.7% of the current. -Agatoxin ( -Aga)-IVA (100 nM) did not produce any effect. Neurotensin inhibition of the whole cell Ca 2+ current was attenuated by each of these treatments except for the -Aga-IVA treatment, which did not change the neurotensin effect. In contrast, neither the -Aga-IVA nor the nimodipine treatment had any effect on the substance-P-induced inhibition; the rest of the treatments attenuated the substance-P-induced response. Thus the data indicate that nucleus basalis neurons express LVA as well as L-, N-, and Q-type, but not the P-type, Ca 2+ currents. N- and Q-type HVA Ca 2+ currents, as well as LVA Ca 2+ currents, are inhibited by both neurotensin and substance P. In contrast, L-type current is inhibited by neurotensin but not by substance P. In addition, a fraction of the total whole cell current was resistant to all Ca 2+ channel antagonists and thus may correspond to the R-type Ca 2+ current. This residual current was inhibited by both neurotensin and substance P. The inhibition of the whole cell Ca 2+ current produced by both