Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+ channels in cultured newborn rat nucleus basalis neurons.

نویسندگان

  • M Margeta-Mitrovic
  • J J Grigg
  • K Koyano
  • Y Nakajima
  • S Nakajima
چکیده

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 microM) 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, omega-conotoxin (omega-CgTx)-GVIA (0.5 microM) inhibited 46.4%, omega-CgTx-GVIA + nimodipine 58.7%, and omega-CgTx-MVIIC (5 microM) + nimodipine 75.7% of the current. Omega-Agatoxin (omega-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 omega-Aga-IVA treatment, which did not change the neurotensin effect. In contrast, neither the omega-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'-[gamma-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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منابع مشابه

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

Margeta-Mitrovic, Marta, John J. Grigg, Konomi Koyano, Yader, because an excessive increase in the intracellular Ca suko Nakajima, and Shigehiro Nakajima. Neurotensin and subconcentration can lead to cellular degeneration and death stance P inhibit lowand high-voltage-activated Ca channels in (Choi 1988). cultured newborn rat nucleus basalis neurons. J. Neurophysiol. 78: Voltage-gated Ca channe...

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عنوان ژورنال:
  • Journal of neurophysiology

دوره 78 3  شماره 

صفحات  -

تاریخ انتشار 1997