MECHANISMS OF OSCILLATORY ACTIVITY IN GUINEA-PIG NUCLEUS-RETICULARIS THALAMI IN-VITRO - A MAMMALIAN PACEMAKER
MECHANISMS OF OSCILLATORY ACTIVITY IN GUINEA-PIG NUCLEUS-RETICULARIS THALAMI IN-VITRO - A MAMMALIAN PACEMAKER
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DOI：
10.1113/jphysiol.1993.sp019794
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发表时间：
1993-08-01
影响因子：
5.5
通讯作者：
MCCORMICK, DA
中科院分区：
文献类型：
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作者：
BAL, T;MCCORMICK, DA
1.本研究采用离体切片记录方法，对豚鼠丘脑网状核（NRT）细胞外和细胞内单个神经元的节律性爆发放电和单次棘波强直放电的离子机制进行了研究.激活皮层/丘脑传入NRT神经元导致短潜伏期爆发的动作电位，随后可以由一个有节奏的序列的振荡爆发放电。在细胞内，这种振荡活动与交替序列的低阈值Ca 2+尖峰分开后超极化电位。细胞内注射短持续时间的超极化电流脉冲导致了类似的序列的振荡突发放电，这表明这种活动是NRT细胞的固有特性。节律性爆发放电的频率高度依赖于电压和温度，在38摄氏度下，-65至-60 mV时的频率在7-12 Hz之间。此外，在去极化膜电位下，振荡爆发性放电通常伴随着单次锋电位活动的延长尾部。3.应用Na+通道毒物河豚毒素阻断了快速动作电位的产生，但保留了由后超极化电位（AHPs）分离的低阈值Ca 2+峰的节律序列。AHPs的逆转电位为-94 mV，表明它是由K+电导增加介导的。细胞外应用四乙基铵或apamin，或细胞内注射Cs+或Ca 2+螯合剂EGTA，都阻断了Ca 2+峰电位AHP，表明它是由Ca 2+激活的K+电流介导的.阻滞AHP导致缓慢后去极化电位（ADP）显著增强。缓慢ADP只发生在低阈值Ca ~（2+）峰电位产生之后。用Mg 2+或Sr 2+取代细胞外Ca 2+导致慢速ADP的消除。此外，[Mg ~（2+）]o的增加导致低阈值Ca ~（2+）峰的消除。相反，用Ba ~（2+）替代细胞外Ca ~（2+）并不能消除缓慢ADP。这些结果表明ADP可以被Ca 2+或Ba 2+激活，但不能被Mg 2+或Sr 2+激活。用胆碱替代细胞外Na+并不能消除慢ADP，而用N-甲基-D-葡糖胺替代则能消除慢ADP，表明慢ADP能被胆碱+支持，但不能被N-甲基-D-葡糖胺+支持。这两种化学物质都不影响低阈值Ca 2+尖峰。这些结果与由Ca 2+激活的非选择性阳离子（CAN）电流介导的慢ADP一致。应用最大剂量的去甲肾上腺素导致在38 ℃下在30-40 Hz处向高度规则的单峰活动转变，而最大剂量的5-羟色胺或谷氨酸代谢型受体激动剂1 S，3R-1-氨基环戊烷-1，3-二羧酸（ACPD）导致在38 ℃下在55-65 Hz处的峰值放电频率。在细胞内，这种向紧张性放电的转变与膜的去极化和表观输入电导的降低有关。在由5-羟色胺诱导的强直性、单峰活动期间应用河豚毒素导致Na+峰的消除和3-6 mV的膜电位的超极化，表明持续的Na+电流对确定该活动模式期间的动作电位放电频率有实质性贡献。我们认为，网状核神经元具有三种不同的振荡活动模式：（1）慢振荡（0.5-7 Hz）在超极化膜电位上的节律性爆发放电，其产生于低阈值Ca ~（2+）电流和Ca ~（2+）激活的K ~+电流的相互作用;（2）在纺锤波频率范围内（7-12 Hz）的节律性爆发放电，随后是由低阈值Ca ~（2+）相互作用引起的单次锋电位活动的紧张性“尾”电流和apamin敏感的Ca 2+激活的K+电流和Ca 2+激活的非选择性阳离子（CAN）电流的激活;（3）强直性，30-60 Hz单峰电活动，出现在5-HT对静息漏K+电流的最大阻断时，去甲肾上腺素或ACPD，其由参与动作电位产生的电流和持续Na+电流之间的新平衡产生。
1. The ionic mechanisms of rhythmic burst firing and single spike, tonic discharge were investigated with extracellular and intracellular recordings of single neurones in the guinea-pig nucleus reticularis thalami (NRT) maintained as a slice in vitro.2. Activation of cortical/thalamic afferents to NRT neurones resulted in a short latency burst of action potentials which could be followed by a rhythmic sequence of oscillatory burst firing. Intracellularly, this oscillatory activity was associated with an alternating sequence of low threshold Ca2+ spikes separated by after-hyperpolarizing potentials. Intracellular injection of short duration hyperpolarizing current pulses resulted in a similar sequence of oscillatory burst firing, suggesting that this activity is an intrinsic property of NRT cells. The frequency of rhythmic burst firing was highly voltage and temperature dependent and was between 7-12 Hz at -65 to -60 mV at 38-degrees-C. In addition, at depolarized membrane potentials, oscillatory burst firing was typically followed by a prolonged tail of single spike activity.3. Application of the Na+ channel poison tetrodotoxin blocked the generation of fast action potentials, but left intact the rhythmic sequence of low threshold Ca2+ spikes separated by after-hyperpolarizing potentials (AHPs). The reversal potential of the AHPs was -94 mV, suggesting that it was mediated by an increase in K+ conductance. Extracellular application of tetraethylammonium or apamin, or intracellular injection of Cs+ or the Ca2+ chelating agent EGTA, blocked the Ca2+ spike AHP, indicating that it is mediated by a Ca2+-activated K+ current.4. Block of the AHP resulted in the marked enhancement of a slow after-depolarizing potential (ADP). The slow ADP occurred only following the generation of low threshold Ca2+ spikes. Replacement of extracellular Ca2+ with Mg2+ or Sr2+ resulted in an abolition of the slow ADP. In addition, the increase in [Mg2+]o resulted in an abolition of the low threshold Ca2+ spike. In contrast, replacement of extracellular Ca2+ with Ba2+ did not abolish the slow ADP. These results indicate that the ADP can be activated by either Ca2+ or Ba2+, but not by Mg2+ or Sr2+.5. Replacement of extracellular Na+ with choline' did not abolish the slow ADP, while replacement with N-methyl-D-glucamine+ did, indicating that the slow ADP can be supported by choline+, but not by N-methyl-D-glucamine+. Neither chemical affected the low threshold Ca2+ spike. These results are consistent with the slow ADP being mediated by a Ca2+-activated non-selective cation (CAN) current.6. Application of maximal doses of noradrenaline resulted in a shift to highly regular single spike activity at 30-40 Hz at 38-degrees-C, while maximal doses of serotonin or the glutamate metabotropic receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) resulted in peak firing frequencies of 55-65 Hz at 38-degrees-C. Intracellularly, this shift to tonic firing was associated with depolarization of the membrane and a decrease in apparent input conductance.7. Application of tetrodotoxin during tonic, single spike activity induced by serotonin resulted in abolition of Na+ spikes and a hyperpolarization of the membrane potential of 3-6 mV, indicating that the persistent Na+ current contributes substantially to the determination of the frequency of action potential discharge during this mode of activity.8. We suggest that nucleus reticularis neurones possess three distinct modes of oscillatory activity: (1) slow (0.5-7 Hz) rhythmic burst firing at hyperpolarized membrane potentials resulting from the interaction of the low threshold Ca2+ current and a Ca2+-activated K+ current; (2) rhythmic burst firing in the frequency range of spindle waves (7-12 Hz) followed by a tonic 'tail' of single spike activity resulting from the interaction of the low threshold Ca2+ current and an apamin-sensitive, Ca2+-activated K+ current and the activation of a Ca2+-activated non-selective cation (CAN) current; and (3) tonic, 30-60 Hz single spike activity which appears during maximal block of resting, leak K+ current by 5-HT, noradrenaline or ACPD and which results from an new equilibrium between the currents involved in action potential generation and the persistent Na+ current.