1. Properties of voltage- and Ca(2+)-dependent K+ currents were investigated in thirty-four dentate granule cells acutely isolated from the resected hippocampus of eleven patients with therapy-refractory temporal lobe epilepsy (TLE). 2. When intracellular Ca2+ was strongly buffered with 11.5 mM EGTA-1 mM Ca2+ in the recording pipette, K+ currents (IK) with a slow activation and biexponential time-dependent decay could be elicited, which showed a threshold for activation around -30 mV. 3. A contribution of Ca(2+)-dependent K+ currents became apparent with intracellular solution containing 1 mM BAPTA-0.1 mM Ca2+. Superfusion of low-Ca2+ extracellular solution blocked 43% of outward currents in this recording configuration. Outward current components could also be blocked by substituting 5 mM Ba2+ for extracellular Ca2+ (78%), or by application of 100 microM Cd2+ (25%). 4. The Ca(2+)-dependent K+ currents could be pharmacologically subdivided into two components. One component was sensitive to 500 microM tetraethylammmonium (TEA; 41%) and 10 nM charybdotoxin (CTX; 47.2%). The blocking effects of 10 nM CTX and 500 microM TEA were not additive, suggesting that both agents block the same conductance. A second, smaller outward current component was blocked by 50 nM apamin (13%). 5. A transient A-type K+ current could be observed in six neurones and showed a fast monoexponential time-dependent inactivation with a steady-state voltage dependence that was distinct from that of IK. The A-type current was blocked by 4-aminopyridine (4-AP) but not by TEA or low-Ca2+ solution. 6. We conclude that outward currents in human hippocampal dentate granule cells can be separated into at least four types by their kinetic and pharmacological properties. These include at least one voltage-dependent current similar to those observed in mammalian hippocampal neurones, and two Ca(2+)-dependent K+ currents that most probably correspond to SK- and BK-type currents. A classical A-type current could be detected in some patients with Ammon's horn sclerosis (AHS) but not in patients with lesion-associated TLE.
展开▼
机译：1.在从11例难治性颞叶癫痫（TLE）患者的切除海马中急性分离的34个齿状颗粒细胞中研究了依赖电压和Ca（2+）的K +电流的特性。 2.当细胞内Ca2 +在记录移液管中被11.5 mM EGTA-1 mM Ca2 +强烈缓冲时，会引起K +电流（IK）缓慢激活和双指数时间依赖性衰减，这表明激活阈值在-30 mV左右。 3.在含有1 mM BAPTA-0.1 mM Ca2 +的细胞内溶液中，Ca（2+）依赖性K +电流的作用变得明显。在此记录配置中，低Ca2 +细胞外溶液的过度注入阻止了43％的外向电流。通过用5 mM Ba2 +代替细胞外Ca2 +（78％），或应用100 microM Cd2 +（25％），也可以阻止外向电流成分。 4.依赖于Ca（2+）的K +电流可以在药理学上细分为两个部分。一种成分对500 microM的四乙铵（TEA; 41％）和10 nM的甲毒素（CTX; 47.2％）敏感。 10 nM CTX和500 microM TEA的阻滞作用不是累加的，表明这两种药物均会阻滞相同的电导。第二个较小的外向电流成分被50 nM的Apapamin（13％）阻断。 5.可以在六个神经元中观察到瞬时A型K +电流，并表现出快速的单指数时间依赖性失活，其稳态电压依赖性不同于IK。 A型电流被4-氨基吡啶（4-AP）阻断，但未被TEA或低Ca2 +溶液阻断。 6.我们得出结论，人海马齿状颗粒细胞的外向电流可以通过其动力学和药理特性分为至少四种类型。这些包括至少一个类似于哺乳动物海马神经元中观察到的电压依赖性电流，以及两个最可能对应于SK型和BK型电流的Ca（2+）依赖性K +电流。在某些Ammon角硬化症（AHS）患者中可以检测到经典A型电流，而在与病变相关的TLE患者中则不能检测到。
展开▼
