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Novel tetrodotoxin-sensitive Ca^<2+> current in mammalian neurons - function and distribution

哺乳动物神经元中新型河豚毒素敏感 Ca^<2> 电流 - 功能和分布

基本信息

批准号：
02404022
负责人：
AKAIKE Norio
金额：
$ 4.03万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02404022/
关键词：
rat hippocampal CA1 region isolated pyramidal neuron tetrodotoxin-sensitive Ca current divalent cation permeability scorpion toxin heterogeneous distribution kinetics lidocaine ラット海馬CA1領域 TTX感受性Ca電流単離錐体細胞電気生理学

项目摘要

1. Voltage-dependent Ca^<2+> currents (I_<Ca>s) in neurons can be classified into T-, N-and L-types. In the CA1 pyramidal neurons freshly dissociated from rat hippocampus we found an additional tetrodotoxin (TTX) -sensitive Ca^<2+> current (termed 'TTX-I_<Ca>'). The TTX-I_<Ca> showed a heterogeneous distribution, preferentially in the dorsal site of CA1 region.2. Activation and inactivation processes of the TTX-I_<Ca> were highly potential-dependent, and the latter was fitted by a double exponential function. The TTX-I_<Ca> was activated at a threshold potential of about-55 mV and reached full activation at-30 mV. The steady-state inactivation of TTX-I_<Ca> could be fitted by a Boltzmann equation with slope factor of 6.0 mV and a half-inactivation voltage of-72.5 mV.3. When the peak amplitudes of TTX-I_<Ca> were plotted as a function of extracellular Ca^<2+> concentration ([Ca^<2+>]_o), the current amplitude increased linearly without showing any saturation.4. The ratio of peak amplitude in the individual I-V relationships of Ca^<2+>, Si^<2+> and Ba^<2+> currents passing through the TTX-sensitive Ca^<2+>-conducting channel was 1 : 0.33 : 0.05, although the current kinetics were much the same.5. TTX inhibited the TTX-I_<Ca> in time and concentration-dependent manner without affecting the current kietics. Lignocaine inhibited the TTX-I_<Ca> in a second in a concentration-dependent manner, with accelerating the inactivation process. The concentrations of half-inhibition (IC_<50>) were 3.5x10^<-9>M for TTX and 3.6x10^<-4>M for lignocaine.6. Scorpion toxin prolonged the inactivation phase of TTX-I_<Ca> in a time-and concentration-dependent manner. In the toxin-treated neurons, both the slow time constant of inactivation (tau_<is>) and its functional contribution to the total current increased with increasing the toxin concentration.

1.神经元电压依赖性钙电流（I_<Ca>s）可分为T型、N型和L型。在从大鼠海马新鲜分离的CA 1锥体神经元中，我们发现了一个额外的河豚毒素（TTX）敏感性Ca^2+电流（称为“TTX-I_<Ca>”）。TTX-I_2<Ca>在脑组织中呈不均匀性分布，以CA 1区背侧为主. TTX-I_2的激活和失活过程<Ca>均具有高度的电位依赖性，后者符合双指数函数。TTX-I_<Ca>在约-55 mV的阈值电位下被激活，并在-30 mV时达到完全激活。TTX-I_的稳态失活<Ca>可以用Boltzmann方程拟合，斜率因子为6.0 mV，半失活电压为-72.5 mV。3.将TTX-I_2的峰值幅度<Ca>与细胞外Ca^<2+>浓度（[Ca^<2+>]_o）作图，电流幅度线性增加，无饱和现象.在通过TTX敏感性Ca^2 +-传导通道的Ca^2+、Si^2+和Ba^2+电流的个别I-V关系中，峰值幅度比为1：0.33：0.05，尽管电流动力学基本相同。TTX呈<Ca>时间和浓度依赖性地抑制TTX-I_2，但不影响电流动力学。Lactobacillus对TTX-I_2的抑制作用<Ca>呈浓度依赖性，并加速了TTX-I_2的灭活过程。TTX和利多卡因的半抑制浓度（IC_<50>）分别为3.5 × 10 - <-9>4 μ M和3.6 × 10 - 4 μ <-4>M。蝎毒素可延长TTX-I_2的失活期，并<Ca>呈时间和浓度依赖性。在毒素处理的神经元中，慢失活时间常数（tau_<is>）及其对总电流的功能贡献均随毒素浓度的增加而增加。