Endogenous pacemaker activity of rat tumour somatotrophs
Endogenous pacemaker activity of rat tumour somatotrophs
复制标题
大鼠肿瘤生长激素的内源性起搏活性
DOI：
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复制
发表时间：
1998
期刊：
影响因子：
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通讯作者：
C. Hammond
中科院分区：
文献类型：
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作者：
R. Kwiecien;C. Robert;R. Cannon;S. Vigues;A. Arnoux;C. Kordon;C. Hammond
1来自大鼠垂体瘤(GC细胞系)的细胞持续释放生长激素，表现为内源性起搏器的作用。同时在膜片钳记录和细胞内钙离子浓度([Ca~(2+))]i成像中，它们显示节律性动作电位(44.7±2.7 mV，178±40ms，0.30±0.0 4 Hz)和伴随的[Ca~(2+)]i瞬变(374±5 7 nM，1.0±0.2 S，0.2 7±0.0 3 Hz)。2去外源性钙离子、加入硝苯地平(1μM)或镍离子(40μM)可可逆地阻断动作电位和[Ca~(2+)]i瞬变，但对河豚毒素(1μM)不敏感。激活于-33.6±0.4 mV(保持电位，-40 mV)的L型钙电流，峰值为-1.8±1.3 mV，可被硝苯地平降低，并被S-(+)-SDZ202791增强。在-41.7±2.7 mV(VH，-80或-60 mV)激活的T/R型钙电流，峰值在-9.2±3.0 mV，可被低浓度的Ni~(2+)(40μM)或Cd~(2+)(10μM)抑制，且具有抗毒素作用。平行实验显示E类钙通道α1亚单位基因的表达。3钾离子通道阻滞剂TEA(25 MM)和河豚毒素(10-100 nM)可增加动作电位的波幅和(或)时程。阿帕明(100 NM)对后峰超极化也有明显的抑制作用。模拟动作电位的去极化步骤所诱发的外向K+尾电流在-6 9.8±0.3 mV处反转，呈现两个分量，持续2~3个S，并被Cd~(2+)(40 0μM)完全阻断。4隔开连续棘波的慢起搏除极(3.5±0.4 S)对应的膜电阻增加2~3倍，对Na+强烈敏感，对河豚毒素不敏感。5计算机模拟表明，起搏器的活动至少可以由6种电流来复制：动作电位的上升相由延迟整流和钙激活的钾电流重新极化，而L型钙电流是动作电位上升相的基础。在棘波之间，钙激活的K+电流和持续的内向阳离子电流的衰减使膜去极化，激活T/R型钙电流，并启动新的周期。
1 Cells derived from a rat pituitary tumour (GC cell line) that continuously release growth hormone behave as endogenous pacemakers. In simultaneous patch clamp recordings and cytosolic Ca2+ concentration ([Ca2+]i) imaging, they displayed rhythmic action potentials (44.7 ± 2.7 mV, 178 ± 40 ms, 0.30 ± 0.04 Hz) and concomitant [Ca2+]i transients (374 ± 57 nM, 1.0 ± 0.2 s, 0.27 ± 0.03 Hz). 2 Action potentials and [Ca2+]i transients were reversibly blocked by removal of external Ca2+, addition of nifedipine (1 μM) or Ni2+ (40 μM), but were insensitive to TTX (1 μM). An L‐type Ca2+ current activated at ‐33.6 ± 0.4 mV (holding potential (Vh), ‐40 mV), peaked at ‐1.8 ± 1.3 mV, was reduced by nifedipine and enhanced by S‐(+)‐SDZ 202 791. A T/R‐type Ca2+ current activated at ‐41.7 ± 2.7 mV (Vh, ‐80 or ‐60 mV), peaked at ‐9.2 ± 3.0 mV, was reduced by low concentrations of Ni2+ (40 μM) or Cd2+ (10 μM) and was toxin resistant. Parallel experiments revealed the expression of the class E calcium channel α1‐subunit mRNA. 3 The K+ channel blockers TEA (25 mM) and charybdotoxin (10‐100 nM) enhanced spike amplitude and/or duration. Apamin (100 nM) also strongly reduced the after‐spike hyperpolarization. The outward K+ tail current evoked by a depolarizing step that mimicked an action potential reversed at ‐69.8 ± 0.3 mV, presented two components, lasted 2‐3 s and was totally blocked by Cd2+ (400 μM). 4 The slow pacemaker depolarization (3.5 ± 0.4 s) that separated consecutive spikes corresponded to a 2‐ to 3‐fold increase in membrane resistance, was strongly Na+ sensitive but TTX insensitive. 5 Computer simulations showed that pacemaker activity can be reproduced by a minimum of six currents: an L‐type Ca2+ current underlies the rising phase of action potentials that are repolarized by a delayed rectifier and Ca2+‐activated K+ currents. In between spikes, the decay of Ca2+‐activated K+ currents and a persistent inward cationic current depolarize the membrane, activate the T/R‐type Ca2+ current and initiate a new cycle.
神经元 α 1E 钙通道亚型的结构和功能特征。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Williams,ME;Marubio,LM;Deal,CR;Hans,M;Brust,PF;Philipson,LH;Miller,RJ;Johnson,EC;Harpold,MM;Ellis,SB
通讯作者：
Ellis,SB