Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.
Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.
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DOI：
10.1016/j.neuroscience.2011.06.028
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发表时间：
2011-09-29
期刊：
影响因子：
3.3
通讯作者：
Brenner, R.
中科院分区：
文献类型：
--
作者：
Jaffe, D. B.;Wang, B.;Brenner, R.
BK通道是Ca2+和电压门控电导，在许多类型的神经元中负责形成动作电位波形。II型BK通道与I型通道的区别在于它们的药理学和慢门控动力学。β4附属亚基在BK α亚基上具有II型性质。在生理离子条件下，利用异源表达系统获得了含和不含β4辅助亚基的BK通道的经验推导性质。这些数据随后被用于研究BK通道单独（I型）和附属β4亚基（II型）如何调节生物物理神经元模型中的动作电位特性。总的来说，这些模型支持这样的假设，即β4亚基提供的较慢动力学使BK通道具有II型特性，从而导致动作电位的扩大，其次，SK通道的更多募集降低了神经元的兴奋性。参数空间的两个区域区分了II型和I型效应；一组bk -激活Ca2+的范围高（约20µM），另一组bk -激活Ca2+的范围低（约0.4 ~ 1.2µM）。后者需要升高的BK通道密度，可能超出可能的生理范围。bk介导的尖峰波形锐化与β4亚基缺乏相关，由于电致效应对尖峰持续时间的影响，bk对电压门控Ca2+通道的特性很敏感。我们还发现，根据Ca2+动力学，II型BK通道可能有能力促进介质AHP，这一特性通常不属于BK通道，影响频率-电流关系。最后，我们展示了II型BK通道所带来的动作电位的扩大也可以间接增加sk型通道的募集，从而降低神经元的兴奋性。
The BK channel is a Ca2+ and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca2+ was high (>20 µM) and the other where BK-activating Ca2+ was low (~0.4–1.2 µM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca2+ channels due to electrogenic effects on spike duration. We also found that depending on Ca2+ dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.
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影响因子：
3.3
作者：
Kaufmann, W. A.;Kasugai, Y.;Ferraguti, F.;Storm, J. F.
通讯作者：
Storm, J. F.
影响因子：
2
作者：
Matthews, Elizabeth A.;Disterhoft, John F.
通讯作者：
Disterhoft, John F.
影响因子：
1.2
作者：
Aradi, I;Holmes, WR
通讯作者：
Holmes, WR
影响因子：
2.5
作者：
Gittis, Aryn H.;Moghadam, Setareh H.;du Lac, Sascha
通讯作者：
du Lac, Sascha
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW