NONSELECTIVE CATION CHANNELS COUPLED WITH TACHYKININ RECEPTORS IN RAT SENSORY NEURONS

NONSELECTIVE CATION CHANNELS COUPLED WITH TACHYKININ RECEPTORS IN RAT SENSORY NEURONS
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DOI:
10.1152/jn.1995.73.2.736
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发表时间:
1995-02-01
影响因子:
2.5
通讯作者:
FUJIMORI, K
FUJIMORI, K
中科院分区:
医学3区
文献类型:
--
作者:
INOUE, K;NAKAZAWA, K;FUJIMORI, K

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1.采用全细胞电压钳技术研究了P物质(SP)等速激肽对大鼠背根神经节感觉神经元膜电流的影响. SP(100 nM)在负电位下在三分之二的细胞中诱发内向电流。在大多数响应SP产生内向电流的细胞中,辣椒素也激活了内向电流。电流在加载有2 mM鸟苷5 '-O-(2-硫代二磷酸)(GDP β S)的细胞中未观察到SP诱发的内向电流。神经激肽A(NKA)或神经激肽B(NKB)也激活内向电流。在每种激动剂100 nM时,激活电流幅度的顺序为NKB > NKA > SP。用含有140 mM NaCl的标准细胞外溶液在+10 mV左右逆转速激肽激活电流。当用蔗糖替代降低细胞外NaCl时,逆转电位变得更负。在含有Cs+、四乙基铵(TEA)或N-甲基-D-葡糖胺(NMDG)作为主要阳离子而不是Na+的细胞外溶液中,内向电流也被激活。由电流的反转电位确定的渗透性的顺序为Cs+除以Na+ > TEA > NMDG。Cs+、TEA或NMDG替代细胞外Na+后,NKB激活的内向电流幅度增加.使用含有Ca 2+作为唯一阳离子的细胞外溶液(外部111.8mM Ca 2+)测试Ca 2(+)的渗透性。在此条件下,NKB诱发了一个内向电流,在+30 mV左右反转。结果表明,SP和其他速激肽激活非选择性阳离子通道,这也是通过受体,这是更敏感的NKB比或NKA的Ca 2+渗透。通道激活可能是感觉神经元中速激肽介导的兴奋性神经传递的一种机制。
1. Effects of substance P (SP) and other tachykinins on membrane currents were investigated using whole cell voltage clamp in cultured sensory neurons isolated from rat dorsal root ganglia.2. SP (100 nM) evoked an inward current in two-thirds of the cells at negative potentials Inmost of the cells that generated the inward current in response to SP, capsaicin also activated an inward. current. The SP-evoked inward current was not observed in cells loaded with 2 mM guanosine 5'-O-( 2-thiodiphosphate) (GDP beta S).3. Neurokinin A (NKA) or neurokinin B (NKB) also activated an inward current. At 100 nM of each agonist, the order was NKB > NKA > SP with respect to activated current amplitude.4. The tachykinin-activated current was reversed around +10 mV with a standard extracellular solution containing 140 mM NaCl. The reversal potential became more negative when extracellular NaCl was reduced by substituting with sucrose. The inward current was also activated in cells bathed in an extracellular solution containing Cs+, tetraethylammonium (TEA) or N-methyl-D-glucamine (NMDG) as a major cation instead of Na+. The order of permeability, determined from the reversal potential of the current, was Cs+ divided by Na+ > TEA > NMDG. The amplitude of the inward current activated by NKB was increased when extracellular Na+ was replaced with Cs+, TEA or NMDG.5. Permeability of Ca2(+) was tested using an extracellular solution containing Ca2+ as the only cation (111.8 mM Ca2+ outside). Under this condition, NKB evoked an inward current that reversed around +30 mV.6. The results suggest that SP and other tachykinins activate nonselective cation channels, which are also permeable to Ca2+ through receptors which are more responsive to NKB than to or NKA. The channel activation may serve as a mechanism underlying tachykinin-mediated excitatory neurotransmission in sensory neurons.