The large conductance calcium-activated potassium (BK) channel is a critical regulator of neuronal action potential firing and follows two distinct trends in early postnatal development: an increase in total expression and a shift from the faster activating STREX isoform to the slower ZERO isoform. We analyzed the functional consequences of developmental trends in BK channel expression in hippocampal neurons isolated from neonatal rats aged one to seven days. Following overnight cultures, action potentials and currents were recorded using whole-cell patch clamp electrophysiology. These neurons undergo a steady increase in excitability during this time and the effect of blockade of BK channel activity with 100 nM iberiotoxin, changes as the neurons mature. BK currents contribute significantly more to total potassium current and single action potentials in neurons of one-day old rats (with BK blockade extending action potential duration by 0.46±0.12 ms) than in those of seven-day old rats (with BK blockade extending action potential duration by 0.17±0.05 ms). BK currents contribute consistently to maintain firing rates in neurons of one-day old rats throughout extended action potential firing; BK blockade evenly depresses firing frequency across action potential trains. In neurons from seven-day old rats, BK blockade initially increases firing frequency and then progressively decreases frequency as firing continues, ultimately depressing neuronal firing rates to a greater extent than in the neurons from one day old animals. These results are consistent with a transition from low expression of a fast activating BK isoform (STREX) to high expression of a slower activating isoform (ZERO).

中文翻译：

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随着大鼠海马神经元在出生后第一周成熟，BK 钾电流对动作电位波形和放电率的贡献不同。

大电导钙激活钾 (BK) 通道是神经元动作电位放电的关键调节器，在出生后早期发育中遵循两种不同的趋势：总表达增加和从较快激活的 STREX 同种型转变为较慢的零同种型。我们分析了从 1 至 7 天大的新生大鼠中分离出的海马神经元中 BK 通道表达的发育趋势的功能后果。在过夜培养后，使用全细胞膜片钳电生理学记录动作电位和电流。在此期间，这些神经元的兴奋性稳步增加，100 nM iberiotoxin 阻断 BK 通道活性的效果随着神经元的成熟而变化。BK 电流对 1 日龄大鼠（BK 阻断延长动作电位持续时间 0.46±0.12 ms）的神经元总钾电流和单动作电位的贡献显着高于 7 日龄大鼠（BK 阻断延长动作）电位持续时间为 0.17±0.05 毫秒）。BK 电流始终有助于维持一天大的大鼠神经元在整个动作电位放电过程中的放电率；BK 阻断均匀地降低了动作电位序列的发射频率。在 7 日龄大鼠的神经元中，BK 阻断剂最初会增加放电频率，然后随着放电的继续而逐渐降低频率，最终比 1 日龄大鼠的神经元更能抑制神经元放电率。