The Journal of Neurophysiology Vol. 78 No. 3 September 1997, pp. 1341-1352
Copyright ©1997 The American Physiological Society

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

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 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, -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 Ca²⁺ 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, 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-[-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.

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