MUSCARINIC SUPPRESSION OF THE M-CURRENT IN THE RAT SYMPATHETIC-GANGLION IS MEDIATED BY RECEPTORS OF THE M1-SUBTYPE
MUSCARINIC SUPPRESSION OF THE M-CURRENT IN THE RAT SYMPATHETIC-GANGLION IS MEDIATED BY RECEPTORS OF THE M1-SUBTYPE
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DOI：
10.1111/j.1476-5381.1989.tb12630.x
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发表时间：
1989-10-01
影响因子：
7.3
通讯作者：
BROWN, DA
中科院分区：
文献类型：
--
作者：
MARRION, NV;SMART, TG;BROWN, DA
在电压箝位下，分离的成年和胎儿大鼠颈上神经节（s.c.g）细胞表现出K+电流的非失活电压或时间依赖性成分，称为m电流（IM）。从预激活IM的电位施加的超极化电压阶跃期间的电流衰减中检测和测量IM。从洗浴液中省略Ca后，静息膜电流和这些电流衰减弛豫的振幅都没有降低，这表明m电流不是依赖于初级Ca内流的“Ca激活”k电流。（+）-管curarine浓度足以阻断缓慢的ca激活的k电流IAHP，但对IAHP没有抑制作用。四乙基铵（1mm）阻断了快速ca激活的k电流IC，对IM产生了小的抑制作用。这是由于毒蕈碱激动剂不能持续阻断IC，从而使IM受到IC污染。毒蕈碱激动剂毒蕈碱、氧tremorine、McN-A-343和甲胆碱可逆地抑制IM，导致向内（去极化）电流。效价排序为：羟戊酸、戊酸、戊酸。muscarine > McN-A-343 >甲胆碱。在成人和胎儿组织培养的细胞中，毒蕈碱对IM的抑制作用与在完整神经节中观察到的相似。吡仑氮平（Pz）和AF-DX 116可抑制毒蕈碱对im的抑制作用，平均pKB值为7.53 +-。0.13 （n = 3）和6.02。0.13 （n = 4）。胆碱激动剂对IM的抑制作用不受胆碱（10-30 μ m）的影响。在300 nM处，4-二苯基乙酰氧基- n -甲基哌啶对反应有抑制作用。吡renzepin对豚鼠离体回肠肌碱产生的收缩有抑制作用，平均pKB为6.37 +-。0.03 （n = 8）。这些结果表明，介导m电流抑制的受体与药理学上指定的M1受体一致，这些受体在大鼠s.c.g.发育的早期阶段就成熟了。
Under voltage-clamp dissociated adult and foetal rat superior cervical ganglion (s.c.g.) cells exhibited a non-inactivating voltage- or time-dependent component of K+ current termed the M-current (IM). IM was detected and measured from the current decay during hyperpolarizing voltage steps applied from potentials where IM was pre-activated. Neither the resting membrane current nor the amplitude of these current decay relaxations were reduced by omitting Ca from the bathing fluid, showing that the M-current was not a ''Ca-activated'' K-current dependent on a primary Ca-influx. Concentrations of (+)-tubocurarine sufficient to block the slow Ca-activated K-current IAHP did not inhibit IAHP. Tetraethylammonium (1 mM), which blocks the fast Ca-activated K-current IC, produced a small inhibition of IM. This was due to contamination of IM by IC since muscarinic agonists did not consistently block IC. The muscarinic agonists muscarine, oxotremorine, McN-A-343 and methacholine reversibly suppressed IM, resulting in an inward (depolarizing) current. The rank order of potency was: oxotremorine .gtoreq. muscarine > McN-A-343 > methacholine. The suppression of IM by muscarine was similar in cultured cells derived from adult and foetal tissue to that seen in the intact ganglia. IM-suppression by muscarine was inhibited by pirenzepine (Pz) and AF-DX 116 with mean pKB values of 7.53 .+-. 0.13 (n = 3) and 6.02 .+-. 0.13 (n = 4) respectively. The suppression of IM by muscarinic agonists was not affected by gallamine (10-30 .mu.M). 4-Diphenylacetoxy-N-methylpiperidine methiodide inhibited the response at 300 nM. Pirenzepine inhibited the contractions of the guinea-pig isolated ileum produced by muscarine with a mean pKB of 6.37 .+-. 0.03 (n = 8). These results suggest that the receptors mediating suppression of the M-current accord with those designated pharmacologically as M1 and that these receptors reach maturity at a very early stage in the development of the rat s.c.g.