Ionic mechanisms of muscarinic depolarization in entorhinal cortex layer II neurons
Ionic mechanisms of muscarinic depolarization in entorhinal cortex layer II neurons
复制标题
DOI：
10.1152/jn.1997.77.4.1829
复制
发表时间：
1997-04-01
影响因子：
2.5
通讯作者：
Alonso, A
中科院分区：
文献类型：
--
作者：
Klink, R;Alonso, A
用细胞内记录和压力脉冲施加卡巴胆碱(CCH)的方法，在组织切片上研究了内侧内嗅皮层第II层星状细胞(SCs)和非星状细胞(NSCs)的直接M胆碱去极化反应的机制。当与触发细胞放电的短DC去极化配对时，亚阈值CCH去极化在幅度和持续时间上得到很大程度的增强。在Na+电导阻断过程中，短暂的直流去极化也增强了CCH的去极化，允许钙离子内流，并且非SCs的增强作用比SCs更强。此外，在非SCs中，CCH去极化可能伴随着慢频率的尖峰电压振荡。在SCS和非SCS中，电压-电流(V-I)关系同样受到CCH的影响，这导致在整个电压范围内稳态V-I关系左移，并在电位为-70 mV左右时增加了表观斜率输入电阻。被钙离子内流增强的CCH反应显示，与非增强反应相比，在电位为-75 mV左右时，斜率输入电阻选择性增加。细胞内注入Cs+(3M)和细胞外注入Ba2+(1 MM)阻断K+电导既不能消除CCH去极化，也不能使CCH对V-I关系产生明显的影响。CCH去极化也不被阻断胞外Cs+的时间依赖性内向整流i-h所减弱。然而，用含Cd~(2+)、Co~(2+)或Mn~(2+)的低钙(0.5 mM)溶液阻断细胞内钙离子的去极化，以及用双-(奥米隆-氨基苯氧基)-N，N，N‘，N’-四乙酸络合胞内钙离子，CCH的去极化作用被取消。用毒毛花素抑制Na+-K+-ATPase可导致更大的CCH去极化。另一方面，当N-甲基-D-葡萄糖胺取代氯化钠时，CCH的去极化作用大大减弱。CCH反应可被0.8 mU的吡仑西平阻断，而六氢地非尼多盐酸盐、对氟类似物(p-F-HHSiD)和亨巴林仅在5-10倍的浓度下才能有效地拮抗CCH。我们的数据与CCH去极化是一致的，在SCs和非SCs中，CCH去极化都是通过激活依赖于钙的阳离子电导的M1受体来介导的，这种阳离子电导基本上可以通透到Na+。这种电导的激活是通过激活触发钙内流的活动而以电压依赖的方式增强的。这一特性实现了一种类似Hebbian的机制，在这种机制下，如果与突触后细胞的活动相结合，毒碱受体的激活可能只会转化为实质性的膜去极化。鉴于内嗅皮层在学习和记忆中的作用，以及在颞叶癫痫等病理中的作用，这种机制可能非常重要。
The mechanisms underlying direct muscarinic depolarizing responses in the stellate cells (SCs) and non-SCs of medial entorhinal cortex layer II were investigated in tissue slices by intracellular recording and pressure-pulse applications of carbachol (CCh). Subthreshold CCh depolarizations were largely potentiated in amplitude and duration when paired with a short DC depolarization that triggered cell firing. During Na+ conductance block, CCh depolarizations were also potentiated by a brief DC depolarization that allowed Ca2+ influx and the potentiation was more robust in non-SCs than in SCs. Also, in non-SCs, CCh depolarizations could be accompanied by spikelike voltage oscillations at a slow frequency. In both SCs and non-SCs, the voltage-current (V-I) relations were similarly affected by CCh, which caused a shift to the left of the steady-state V-I relations over the entire voltage range and an increase in apparent slope input resistance at potentials positive to about -70 mV. CCh responses potentiated by Ca2+ influx demonstrated a selective increase in slope input resistance at potentials positive to about -75 mV in relation to the nonpotentiated responses. K+ conductance block with intracellular injection of Cs+ (3 M) and extracellular Ba2+ (1 mM) neither abolished CCh depolarizations nor resulted in any qualitatively distinct effect of CCh on the V-I relations. CCh depolarizations were also undiminished by block of the time-dependent inward rectifier I-h with extracellular Cs+. However, CCh depolarizations were abolished during Ca2+ conductance block with low-Ca2+ (0.5 mM) solutions containing Cd2+, Co2+, or Mn2+, as well as by intracellular Ca2+ chelation with bis-(omicron-aminophenoxy)-N,N,N',N'-tetraacetic acid. Inhibition of the Na+ -K+ ATPase with strophanthidin resulted in larger CCh depolarizations. On the other hand, when NaCl was replaced by N-methyl-D-glucamine, CCh depolarizations were largely diminished. CCh responses were blocked by 0.8 mu M pirenzepine, whereas hexahydro-sila-difenidol-hydrochloride, p-fluoroanalog (p-F-HHSiD) and himbacine were only effective antagonists at 5- to 10-fold larger concentrations. Our data are consistent with CCh depolarizations being mediated in both SCs and non-SCs by ml receptor activation of a Ca2+ dependent cationic conductance largely permeable to Na+. Activation of this conductance is potentiated in a voltage-dependent manner by activity triggering Ca2+ influx. This property implements a Hebbian-like mechanism whereby muscarinic receptor activation may only be translated into substantial membrane depolarization if coupled to postsynaptic cell activity. Such a mechanism could be highly significant in light of the role of the entorhinal cortex in learning and memory as well as in pathologies such as temporal lobe epilepsy.