Campbell L W, Hao S Y, Thibault O, Blalock E M, Landfield P W
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington 40536, USA.
J Neurosci. 1996 Oct 1;16(19):6286-95. doi: 10.1523/JNEUROSCI.16-19-06286.1996.
Previous current-clamp studies in rat hippocampal slice CA1 neurons have found aging-related increases in long-lasting calcium (Ca)-dependent and Ca-mediated potentials. These changes could reflect an increase in Ca influx through voltage-gated Ca channels but also could reflect a change in potassium currents. Moreover, if altered Ca influx is involved, it is nuclear whether it arises from generally increased Ca channel activity, lower threshold, or reduced inactivation. To analyze the basis for altered Ca potentials, whole-cell voltage-clamp studies of CA1 hippocampal neurons were performed in nondissociated hippocampal slices of adult (3- to 5-month-old) and aged (25- to 26-month-old) rats. An aging-related increase was found in high-threshold Ca and barium (Ba) currents, particularly in the less variable, slowly inactivating (late) current at the end of a depolarization step. Input resistance of neurons did not differ between age groups. In steady-state inactivation and repetitive-pulse protocols, inactivation of Ca and Ba currents was not reduced and, in some cases, was slightly greater in aged neurons, apparently because of larger inward current. The current blocked by nimodipine was greater in aged neurons, indicating that some of the aging increase was in L-type currents. These results indicate that whole-cell Ca currents are increased with aging in CA1 neurons, apparently attributable to greater channel activity rather than to reduced inactivation. The elevated Ca influx seems likely to play a role in impaired function and enhanced susceptibility to neurotoxic influences.
先前对大鼠海马体切片CA1神经元进行的电流钳研究发现，与衰老相关的持久钙（Ca）依赖性和Ca介导电位增加。这些变化可能反映了通过电压门控Ca通道的Ca内流增加，但也可能反映了钾电流的变化。此外，如果涉及改变的Ca内流，那么它是源于普遍增加的Ca通道活性、较低的阈值还是减少的失活尚不清楚。为了分析Ca电位改变的基础，在成年（3至5个月大）和老年（25至26个月大）大鼠的未分离海马体切片中对CA1海马神经元进行了全细胞电压钳研究。发现高阈值Ca和钡（Ba）电流存在与衰老相关的增加，特别是在去极化步骤结束时变化较小、缓慢失活（晚期）电流中。各年龄组神经元的输入电阻没有差异。在稳态失活和重复脉冲实验中，Ca和Ba电流的失活没有降低，在某些情况下，老年神经元中的失活略有增加，显然是因为内向电流更大。老年神经元中被尼莫地平阻断的电流更大，表明衰老增加的部分是L型电流。这些结果表明，CA1神经元中的全细胞Ca电流随衰老而增加，显然是由于通道活性增加而非失活减少。Ca内流升高似乎可能在功能受损和对神经毒性影响易感性增强中起作用。
