VOLTAGE-GATED POTASSIUM CURRENTS IN ACUTELY DISSOCIATED RAT CORTICAL-NEURONS
VOLTAGE-GATED POTASSIUM CURRENTS IN ACUTELY DISSOCIATED RAT CORTICAL-NEURONS
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DOI：
10.1152/jn.1993.70.1.51
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发表时间：
1993-07-01
影响因子：
2.5
通讯作者：
SURMEIER, DJ
中科院分区：
文献类型：
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作者：
FOEHRING, RC;SURMEIER, DJ
1.在失活动力学和电压依赖性的基础上，我们描述了急性分离的大鼠感觉运动皮层神经元的三种外向K+电流成分.快A电流（I（Af））在-40 mV时完全失活，在-52 mV时半失活。它迅速激活[在-10 mV时达峰时间（TTP）8 ms]并灭活（在-10 mV时tau（无效）= 12 ms）。在-100 mV下，失活恢复的时间常数约为80 ms。它对四乙基铵（TEA）和树毒素不敏感，但可被4-氨基吡啶（4-AP，IC 50 = 1 mM）阻断.缓慢失活电流（I（Ks））是在急性分离的成年神经元中观察到的最大电流。它在-40 mV时完全失活，在-98 mV时半失活，并且动力学上比快A电流慢（在-10 mV时TTP = 130 ms;在-10 mV时tau（inact）= 293 ms）。失活尾部用时间常数为2-10和15-40 ms的两个指数之和拟合。在-100 mV下，从失活中回收的I（KS）的时间常数约为1，200 ms。有两种组分以更慢的动力学失活。极缓慢失活电流（I（KSS））在操作上定义为在-40 mV下保持5 s后剩余的电流。一个组件在-10 mV下失活，时间常数为1，927 ms。另一个组件在5秒测试命令内未显示失活，但在40至50秒的步长内达到-10 mV，在约20秒的tau下失活。非常缓慢的失活电流以与I（KS）类似的动力学激活（在-10 mV下TTP = 121 ms），并且在保持在-40 mV后观察到两个失活尾部，其动力学类似于在-100 mV预脉冲后的那些。I（KS）和I（KSS）对TEA敏感。百分之七十六（76%）的I（KSS）被30 mM TEA阻断。对于I（KSS），存在TEA阻断的两种组分，IC 50为88 μ M（可阻断电流的67%）和7 mM（33%）。百分之七十（70%）的I（KS）被30 mM TEA阻断。对于I（KS）电流，也有两种有效浓度，IC 50为8 μ M（可阻断电流的21%）和3 mM（79%）。I（KS）和I（KSS）对4-AP敏感。百分之七十六（76%）的I（KSS）被3-5 mM 4-AP阻断。I（KSS）呈4-AP阻滞的两个成分。高亲和力组分的IC 50为90 μ M（66%的可阻断电流），低亲和力组分的IC 50为7 mM（34%的电流）。只有24%的I（KS）对3-5 mM的4-AP敏感。通过92 μ M的单个IC 50很好地拟合该区块。I（KS）和I（KSS）也对树毒素敏感。I（KSS）被100 nM树毒素阻断（100%阻断）。I（KSS）表现出两种成分的树状毒素阻断，IC 50为266 pM（电流的46%）和27 nM（54%）。只有36%的I（KS）被100 nM的树毒素阻断。该阻断有两个成分，IC 50分别为146 pM（可阻断电流的29%）和10.4 nM（电流的71%）。8.讨论了一个模型，其中电压门控K+电流由四种通道类型表示：快速A（A（f）），缓慢失活（K1），和两个非常缓慢失活类型（K2和K3）。
1. We describe three outward K+ current components in acutely dissociated neurons from rat sensorimotor cortex on the basis of inactivation kinetics and voltage dependence.2. The fast A current (I(Af)) was completely inactivated at -40 mV and half-inactivated at -52 mV. It activated [time to peak (TTP) 8 ms at -10 mV] and was inactivated (tau(inact) = 12 ms at -10 mV) rapidly. Recovery from inactivation had a time constant of approximately 80 ms at -100 mV. It was insensitive to tetraethyl ammonium (TEA) and dendrotoxin but was blocked by 4-aminopyridine (4-AP, IC50 = 1 mM).3. The slowly inactivating current (I(Ks)) was the largest current seen in acutely dissociated adult neurons. It was completely inactivated at -40 mV, half-inactivated at -98 mV, and was kinetically slower (TTP = 130 ms at -10 mV; tau(inact) = 293 ms at -10 mV) than the fast A current. Deactivation tails were fit with the sum of two exponentials with time constants of 2-10 and 15-40 ms. I(KS) recovered from inactivation with a time constant of approximately 1,200 ms at -100 mV.4. There were two components that inactivated with even slower kinetics. The very slowly inactivating current (I(KSS)) was operationally defined as the current remaining after a 5-s hold at -40 mV. One component inactivated with a time constant of 1,927 ms at -10 mV. The other component showed no inactivation over a 5-s test command, but in 40- to 50-s steps to -10 mV, inactivated with a tau of approximately 20 s. The very slowly inactivating current activated with similar kinetics to I(KS) (TTP = 121 ms at -10 mV), and two deactivation tails, with kinetics similar to those after the -100 mV prepulse, were observed after holding at -40 mV.5. Both I(KS) and I(KSS) were sensitive to TEA. Seventy-six percent (76%) of I(KSS) was blocked by 30 mM TEA. Two components to the TEA block were present for I(KSS), with IC50s of 88 muM (67% of blockable current) and 7 mM (33%). Seventy percent (70%) of I(KS) was blocked by 30 mM TEA. For the I(KS) current, there were also two effective concentrations, with IC50s of 8 muM (21% of blockable current) and 3 mM (79%).6. I(KS) and I(KSS) were also sensitive to 4-AP. Seventy-six percent (76%) of I(KSS) was blocked by 3-5 mM 4-AP. I(KSS) exhibited two components of 4-AP block. The high-affinity component had an IC50 of 90 muM (66% of blockable current), and the low-affinity component had an IC50 of 7 mM (34% of current). Only 24% of I(KS) was sensitive to 3-5 mM 4-AP. This block was well fit by a single IC50 of 92 muM.7. I(KS) and I(KSS) were also dendrotoxin sensitive. I(KSS) was blocked by 100 nM dendrotoxin (100% block). I(KSS) exhibited two components of dendrotoxin block, with IC50s of 266 pM (46% of current) and 27 nM (54%). Only 36% of I(KS) was blocked by 100 nM dendrotoxin. This block had two components with IC50s of 146 pM (29% of blockable current) and 10.4 nM (71% of current).8. A model is discussed in which the voltage-gated K+ currents are represented by four channel types: fast A (A(f)), slowly inactivating (K1), and two very slowly inactivating types (K2 and K3).