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

1.神经元电压依赖性钙电流可分为T-型、N-型和L型。在刚从大鼠海马区分离出的CA1锥体神经元中，我们发现了一种额外的河豚毒素(TTX)敏感的钙电流(称为TTX-I_&lt；Ca&gt；)。结论：1.TTX-I_&lt；Ca&gt；呈异质性分布，主要分布在CA1区背侧。TTX-I_&lt；Ca&gt；的激活和失活过程是高度依赖于电位的，后者符合双指数函数。TTX-I_&lt；Ca&gt；在阈值电位约为-55 mV时被激活，在-30 mV时达到完全激活。TTX-I&lt；Ca&gt；的稳态失活符合Boltzmann方程，斜率因子为6.0 mV，半失活电压为-72.5 mV.3。当TTX-I_&lt；Ca&gt；的峰值幅度作为细胞外钙浓度([Ca^&lt；2+&gt；]_o)的函数时，电流幅度呈线性增加，没有表现出任何饱和。尽管电流动力学基本相同，但流经TTX敏感钙通道的钙电流、硅离子电流和Ba2+电流的I-V关系峰值之比为1：0.33：0.05。TTX以时间和浓度依赖的方式抑制TTX-I_&lt；Ca&gt；，而不影响电流。Lignocaine对TTX-I_&lt；Ca&gt；的抑制作用呈浓度依赖性，并加速了失活过程。TTX的半数抑制浓度(IC50)为3.5×10~(-9)M，木质素的半数抑制浓度(IC_(50))为3.6×10~(-4)。蝎子毒素以时间和浓度依赖的方式延长TTX-I&lt；Ca&Gt；的失活期。在毒素处理的神经元中，失活慢时间常数及其对总电流的功能贡献均随毒素浓度的增加而增大。

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.