Ly Cheng, Melman Tamar, Barth Alison L, Ermentrout G Bard
Department of Mathematics, University of Pittsburgh, Pittsburgh, PA 15260, USA.
J Comput Neurosci. 2011 Apr;30(2):211-23. doi: 10.1007/s10827-010-0246-3. Epub 2010 Jun 2.
BK channels are large conductance potassium channels gated by calcium and voltage. Paradoxically, blocking these channels has been shown experimentally to increase or decrease the firing rate of neurons, depending on the neural subtype and brain region. The mechanism for how this current can alter the firing rates of different neurons remains poorly understood. Using phase-resetting curve (PRC) theory, we determine when BK channels increase or decrease the firing rates in neural models. The addition of BK currents always decreases the firing rate when the PRC has only a positive region. When the PRC has a negative region (type II), BK currents can increase the firing rate. The influence of BK channels on firing rate in the presence of other conductances, such as I(m) and I(h), as well as with different amplitudes of depolarizing input, were also investigated. These results provide a formal explanation for the apparently contradictory effects of BK channel antagonists on firing rates.
BK通道是由钙和电压门控的大电导钾通道。矛盾的是，实验表明，根据神经亚型和脑区的不同，阻断这些通道会增加或降低神经元的放电频率。关于这种电流如何改变不同神经元放电频率的机制仍知之甚少。利用相位重置曲线（PRC）理论，我们确定了BK通道在神经模型中何时会增加或降低放电频率。当PRC仅具有正区域时，添加BK电流总是会降低放电频率。当PRC具有负区域（II型）时，BK电流可以增加放电频率。我们还研究了在存在其他电导（如I(m)和I(h)）以及不同幅度去极化输入的情况下，BK通道对放电频率的影响。这些结果为BK通道拮抗剂对放电频率的明显矛盾效应提供了一个正式的解释。
