Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, 4400 University Dr. MSN 2A1, Fairfax, VA 22030, USA.
Neurotoxicology. 2013 Jul;37:19-25. doi: 10.1016/j.neuro.2013.03.002. Epub 2013 Mar 21.
ω-Agatoxin-IVA is a well known P/Q-type Ca(2+) channel blocker and has been shown to affect presynaptic Ca(2+) currents as well postsynaptic potentials. P/Q-type voltage gated Ca(2+) channels play a vital role in presynaptic neurotransmitter release and thus play a role in action potential generation. Monitoring spontaneous activity of neuronal networks on microelectrode arrays (MEAs) provides an important tool for examining this neurotoxin. Changes in extracellular action potentials are readily observed and are dependent on synaptic function. Given the efficacy of murine frontal cortex and spinal cord networks to detect neuroactive substances, we investigated the effects of ω-agatoxin on spontaneous action potential firing within these networks. We found that networks derived from spinal cord are more sensitive to the toxin than those from frontal cortex; a concentration of only 10nM produced statistically significant effects on activity from spinal cord networks whereas 50 nM was required to alter activity in frontal cortex networks. Furthermore, the effects of the toxin on frontal cortex are more complex as unit specific responses were observed. These manifested as either a decrease or increase in action potential firing rate which could be statistically separated as unique clusters. Administration of bicuculline, a GABAA inhibitor, isolated a single response to ω-agatoxin, which was characterized by a reduction in network activity. These data support the notion that the two clusters detected with ω-agatoxin exposure represent differential responses from excitatory and inhibitory neuronal populations.
ω-芋螺毒素-IVA 是一种众所周知的 P/Q 型钙 (Ca2+) 通道阻断剂，已被证明会影响突触前 Ca2+电流以及突触后电位。P/Q 型电压门控 Ca2+通道在突触前神经递质释放中起着至关重要的作用，因此在动作电位产生中起着重要作用。监测微电极阵列 (MEA) 上神经元网络的自发活动为检查这种神经毒素提供了重要工具。细胞外动作电位的变化很容易观察到，并且依赖于突触功能。鉴于鼠前额皮质和脊髓网络检测神经活性物质的功效，我们研究了 ω-芋螺毒素对这些网络中自发性动作电位放电的影响。我们发现，源自脊髓的网络比源自前额皮质的网络对毒素更敏感；仅 10 nM 的浓度就会对脊髓网络的活性产生统计学上显著的影响，而 50 nM 的浓度则需要改变前额皮质网络的活性。此外，毒素对前额皮质的影响更为复杂，因为观察到了特定单元的反应。这些表现为动作电位发放率的增加或减少，可以通过统计学方法分为独特的簇。给予 GABAA 抑制剂荷包牡丹碱可分离出对 ω-芋螺毒素的单一反应，其特征是网络活性降低。这些数据支持这样一种观点，即 ω-芋螺毒素暴露检测到的两个簇代表兴奋性和抑制性神经元群体的不同反应。
