Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+ channels in cultured newborn rat nucleus basalis neurons.
Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+ channels in cultured newborn rat nucleus basalis neurons.
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神经降压素和 P 物质抑制培养的新生大鼠基底核神经元中低电压和高电压激活的 Ca2 通道。
DOI：
10.1152/jn.1997.78.3.1341
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Nakajima,S
中科院分区：
文献类型：
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作者：
Margeta-Mitrovic,M;Grigg,JJ;Koyano,K;Nakajima,Y;Nakajima,S
Margeta-Mitrovic，玛尔塔，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.用全细胞膜片钳技术研究了兴奋性神经递质神经降压素和P物质对培养的基底核神经元钙电流的抑制作用。神经降压素和P物质分别对全细胞Ca 2+电流和低电压激活（LVA）Ca 2+电流的抑制率分别为67.9%和57.6%。全细胞Ca 2+电流由维持电位为−80 mV的阶跃脉冲至0 mV引起，在100 ms时测量。低电压激活（LVA）Ca 2+电流由维持电位为−90 mV的阶跃脉冲至−40 mV引起，神经降压素（26.2%）和P物质（24.1%）均能抑制该作用。使用Ca 2+通道拮抗剂分离高电压激活的Ca 2+电流。尼莫地平（3 μM）抑制24.2%的由阶跃至0或+10 mV引起的全细胞钙电流，在相同条件下，ω-芋螺毒素（ω-CgTx）-GVIA（0.5 μM）、ω-CgTx-GVIA +尼莫地平和ω-CgTx-MVIIC（5 μM）+尼莫地平分别抑制46.4%、58.7%和75.7%。ω-Agatoxin（ω-阿加）-IVA（100 nM）未产生任何影响。除ω-Aga-IVA处理不改变神经降压素效应外，这些处理中的每一种都减弱了神经降压素对全细胞Ca 2+电流的抑制。相比之下，ω-Aga-IVA和尼莫地平处理对P物质诱导的抑制没有任何影响;其余处理减弱了P物质诱导的反应。因此，数据表明，基底核神经元表达LVA以及L-，N-和Q-型，但不是P-型，钙电流。N-和Q-型HVA钙电流，以及LVA钙电流，抑制神经降压素和P物质。相反，L-型电流抑制神经降压素，但不是由P物质。此外，一小部分的总全细胞电流是耐所有的钙通道拮抗剂，因此可能对应于R-型钙电流。这种残余电流被神经降压素和P物质抑制。这两种神经递质产生的全细胞Ca 2+电流的抑制是电压无关的，因为大的去极化（+70 mV）不能缓解这两种效应。在加载0.1 mM鸟苷5′-[γ-硫代]三磷酸的细胞中，对神经降压素和P物质的反应变得不可逆，表明两种神经递质的作用都是通过G蛋白介导的。然而，百日咳毒素并不影响神经降压素或P物质的反应。
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.