Department of Pharmacology, The School of Pharmacy, University of London, London, UK.
Nat Neurosci. 2011 Apr;14(4):478-86. doi: 10.1038/nn.2757. Epub 2011 Feb 27.
The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are subthreshold, voltage-gated ion channels that are highly expressed in hippocampal and cortical pyramidal cell dendrites, where they are important for regulating synaptic potential integration and plasticity. We found that HCN1 subunits are also localized to the active zone of mature asymmetric synaptic terminals targeting mouse entorhinal cortical layer III pyramidal neurons. HCN channels inhibited glutamate synaptic release by suppressing the activity of low-threshold voltage-gated T-type (Ca(V)3.2) Ca²(+) channels. Consistent with this, electron microscopy revealed colocalization of presynaptic HCN1 and Ca(V)3.2 subunit. This represents a previously unknown mechanism by which HCN channels regulate synaptic strength and thereby neural information processing and network excitability.
超极化激活环核苷酸门控 (HCN) 通道是阈下电压门控离子通道，在海马和皮质锥体神经元树突中高度表达，对调节突触电位整合和可塑性很重要。我们发现 HCN1 亚基也定位于靶向成熟的不对称突触末端的活性区，这些末端靶向小鼠内嗅皮质层 III 锥体神经元。HCN 通道通过抑制低阈值电压门控 T 型 (Ca(V)3.2) Ca²⁺通道的活性来抑制谷氨酸突触释放。与此一致，电子显微镜显示突触前 HCN1 和 Ca(V)3.2 亚基共定位。这代表了 HCN 通道调节突触强度从而调节神经信息处理和网络兴奋性的一个以前未知的机制。
