MECHANISMS OF ACTION OF ACETYLCHOLINE IN THE GUINEA-PIG CEREBRAL-CORTEX INVITRO
MECHANISMS OF ACTION OF ACETYLCHOLINE IN THE GUINEA-PIG CEREBRAL-CORTEX INVITRO
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DOI：
10.1113/jphysiol.1986.sp016112
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发表时间：
1986-06-01
影响因子：
5.5
通讯作者：
PRINCE, DA
中科院分区：
文献类型：
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作者：
MCCORMICK, DA;PRINCE, DA
应用前扣带回脑片V层锥体细胞的细胞内记录，研究了乙酰胆碱(ACh)在豚鼠新皮质的作用机制。在静止膜电位(Vm=-80~-70 mV)时，ACh引起兴奋性和抑制性突触后电位(p.s.p.s)的一连串变化，并伴随着表观输入阻力(Ri)的降低。ACh作用于锥体神经元去极化至略低于放电阈值(Vm=-65至-55 mV)，可产生短潜伏期超极化伴随PPS和Ri的降低，随后是长时间(10至大于60 S)的去极化和动作电位的产生。这两种反应在推测的其他皮质区域(感觉运动和视觉)的锥体神经元中也被发现，并被毒碱类拮抗剂阻断，但不能被尼古丁类拮抗剂阻断。ACh诱发的超极化的平均翻转电位为-75.8 mV，与伽马氨基丁酸(GABA)超极化反应的平均翻转电位-72.4 mV相似。由顺向刺激产生(-69.6 mV)。这种胆碱能抑制反应可以由ACh在离细胞明显更远的地方引起，而不是缓慢的去极化反应。用含Mn2+和低钙的溶液阻断GABA能突触传递，或局部应用河豚毒素(TTX)、荷包牡丹碱或苦参碱，均可消除ACh诱导的抑制性反应，但不能消除慢的兴奋性反应。在TTX(或Mn2+，低钙)中，慢兴奋反应的最小起始潜伏期为250ms，并与Ri的电压依赖性增加有关。应用ACh可引起8个神经元的短潜伏期兴奋，并伴有Ri降低。这种兴奋的时间进程类似于锥体神经元的抑制。其中七个神经元的动作电位具有异常短暂的持续时间，这表明它们可能是非锥体细胞。ACh阻断慢后超极化(a.h.P.)在一系列动作电位之后，偶尔会以顺向诱发的P.S.P.减少，但对动作电位的宽度或最大上升或下降速度没有影响。结论：胆碱能抑制锥体神经元的作用是通过对非锥体细胞的毒碱兴奋，导致GABA的释放而实现的。在锥体细胞中，ACh引起电压依赖性超极化电导(M-电流)和钙激活的钾电导的相对缓慢的阻断(M-电流在去极化的膜电位上最为活跃)。
The mechanisms of action of acetylcholine (ACh) in the guinea‐pig neocortex were investigated using intracellular recordings from layer V pyramidal cells of the anterior cingulate cortical slice. At resting membrane potential (Vm = ‐80 to ‐70 mV), ACh application resulted in a barrage of excitatory and inhibitory post‐synaptic potentials (p.s.p.s) associated with a decrease in apparent input resistance (Ri). ACh, applied to pyramidal neurones depolarized to just below firing threshold (Vm = ‐65 to ‐55 mV), produced a short‐latency hyperpolarization concomitant with p.s.p.s and a decrease in Ri, followed by a long‐lasting (10 to greater than 60 s) depolarization and action potential generation. Both of these responses were also found in presumed pyramidal neurones of other cortical regions (sensorimotor and visual) and were blocked by muscarinic, but not nicotinic, antagonists. The ACh‐induced hyperpolarization possessed an average reversal potential of ‐75.8 mV, similar to that for the hyperpolarizing response to gamma‐aminobutyric acid (GABA; ‐72.4 mV) and for the i.p.s.p. generated by orthodromic stimulation (‐69.6 mV). This cholinergic inhibitory response could be elicited by ACh applications at significantly greater distance from the cell than the slow depolarizing response. Blockade of GABAergic synaptic transmission with solution containing Mn2+ and low Ca2+, or by local application of tetrodotoxin (TTX), bicuculline or picrotoxin, abolished the ACh‐induced inhibitory response but not the slow excitatory response. In TTX (or Mn2+, low Ca2+) the slow excitatory response possessed a minimum onset latency of 250 ms and was associated with a voltage‐dependent increase in Ri. Application of ACh caused short‐latency excitation associated with a decrease in Ri in eight neurones. The time course of this excitation was similar to that of the inhibition seen in pyramidal neurones. Seven of these neurones had action potentials with unusually brief durations, indicating that they were probably non‐pyramidal cells. ACh blocked the slow after‐hyperpolarization (a.h.p.) following a train of action potentials, occasionally reduced orthodromically evoked p.s.p.s, and had no effect on the width or maximum rate of rise or fall of the action potential. It is concluded that cholinergic inhibition of pyramidal neurones is mediated through a rapid muscarinic excitation of non‐pyramidal cells, resulting in the release of GABA. In pyramidal cells ACh causes a relatively slow blockade of both a voltage‐dependent hyperpolarizing conductance (M‐current) which is most active at depolarized membrane potentials, and the Ca2+‐activated K+ conductance underlying the a.h.p.(ABSTRACT TRUNCATED AT 400 WORDS)