Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+ channels in cultured newborn rat nucleus basalis neurons
| Autor: | Marta Margeta-Mitrovic, Shigehiro Nakajima, Konomi Koyano, John J. Grigg, Yasuko Nakajima |
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| Rok vydání: | 1997 |
| Předmět: |
Patch-Clamp Techniques
Physiology Substance P Nucleus basalis Basal Ganglia Membrane Potentials chemistry.chemical_compound GTP-Binding Proteins Animals Virulence Factors Bordetella Cells Cultured Neurotensin Neurons Chemistry General Neuroscience Calcium Channel Blockers Cell biology Rats Electrophysiology Animals Newborn Pertussis Toxin Ca2 channels Calcium Channels Neuroscience Ion Channel Gating |
| Zdroj: | Journal of neurophysiology. 78(3) |
| ISSN: | 0022-3077 |
| Popis: | Margeta-Mitrovic, Marta, John J. Grigg, Konomi Koyano, Yasuko Nakajima, and Shigehiro Nakajima. Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+channels in cultured newborn rat nucleus basalis neurons. J. Neurophysiol. 78: 1341–1352, 1997. Inhibition of Ca2+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 Ca2+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) Ca2+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 Ca2+currents were separated with the use of the Ca2+channel antagonists. Nimodipine (3 μM) inhibited 24.2% of the whole cell Ca2+current elicited by a step to 0 or +10 mV and measured at 100 ms. Under the same conditions, ω-conotoxin (ω-CgTx)-GVIA (0.5 μM) inhibited 46.4%, ω-CgTx-GVIA + nimodipine 58.7%, and ω-CgTx-MVIIC (5 μM) + nimodipine 75.7% of the current. ω-Agatoxin (ω-Aga)-IVA (100 nM) did not produce any effect. Neurotensin inhibition of the whole cell Ca2+current was attenuated by each of these treatments except for the ω-Aga-IVA treatment, which did not change the neurotensin effect. In contrast, neither the ω-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, Ca2+currents. N- and Q-type HVA Ca2+currents, as well as LVA Ca2+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 Ca2+channel antagonists and thus may correspond to the R-type Ca2+current. This residual current was inhibited by both neurotensin and substance P. The inhibition of the whole cell Ca2+current produced by both neurotransmitters was voltage independent, because a large depolarization (+70 mV) was not able to relieve either effect. In cells loaded with 0.1 mM guanosine 5′-[γ-thio]triphosphate, response to both neurotensin and substance P became irreversible, indicating that the effects of both neurotransmitters were mediated through G proteins. However, pertussis toxin did not affect either the neurotensin or the substance P response. |
| Databáze: | OpenAIRE |
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