Ion channels, epilepsy, depression, dendritic ion channels, axonal ion channels, drug screening, patch clamp, two-electrode recordings
Ion channels have to be at the right place in the right number to endow individual neurons with their specific character. Their biophysical properties together with their spatial distribution define the signaling characteristics of a neuron. Improper channel localization could lead to communication defects in a neuronal network, thus facilitate the generation and development of neurological and psychological disorders. However, because of the limitation of patch-clamping techniques, people used to pay close attention to the ion channels expressed on neuronal soma and ignore the important function of ion channels in neuronal small compartments (NSC, axon, dendrites, spines et al.). Thanks to the development of dendritic and axonal patch-clamping techniques (which are able to record ion channel’s activities from axon and dendrites) combined with calcium and voltage-sensitive dye imaging techniques, people realized that expression and function of ion channels in NSC are largely different from the channels expressed on neuronal soma and these NSC channels normally play a unique role in different compartments. For example, Nav1.2 sodium channels are localized to neuronal apical dendrites which contribute to the action potential back-propagation while Nav1.6 sodium channels are mainly localized to the neuronal axonal initial segment (AIS) and play an important role in the initiation of axon potentials. In addition, some ion channels in NSC have already been identified as a good drug targets, e.g. KCNQ channels in AIS and APMA receptors in dendritic spines. My lab in Peking University utilized dendritic and axonal patch-clamp recordings combined with calcium-sensitive dye two-photon imaging, molecular biology, genetics and pharmacological techniques to uncover the expression and function of ion channels in NSC.
Zhang J, Zhang C, Chen X, Wang B, Ma W, Yang Y, Zheng R*, Huang Z* (2021) PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice. Communication Biology 4(1):263.
Ma Y, Xie H, Du X, Wang L, Jin X, Zhang Q, Han Y, Sun S, Wang L, Li X, Zhang C, Wang M, Li C, Xu J, Huang Z*, Wang X*, Chai Z*, Deng H*. (2021) In vivo chemical reprogramming of astrocytes into neurons. Cell Discovery 7(1):12.
Kong W, Tu X, Huang W, Yang Y, Xie Z* & Huang Z * (2020) Prediction and Optimization of NaV1.7 Sodium Channel Inhibitors Based on Machine Learning and Simulated Annealing. Journal of chemical information and modeling, 60(6), 2739–2753.
Gao M, Kong W, Huang Z* & Xie Z* (2020) Identification of Key Genes Related to Lung Squamous Cell Carcinoma Using Bioinformatics Analysis. International journal of molecular sciences, 21(8), 2994.
Kong W, Gao M, Jin Y, Huang W, Huang Z* & Xie Z* (2020) Prognostic model of patients with liver cancer based on tumor stem cell content and immune process. Aging, 27;12(16):16555-16578
Chi XM, Jin XQ, Chen Y, Lu XL, Tu XY, Li XR, Zhang YY, Lei JL, Huang J, Huang Z*, Zhou Q* and Pan XJ* (2020) Structural insights into the gating mechanism of human SLC26A9 mediated by its C-terminal sequence, Cell Discovery, 6:55
Jin XQ, Chen Q, Song Y, Zheng J, Xiao K, Shao S, Fu ZB, Yi M, Yang Y, and Huang Z* (2019) Dopamine D2 Receptors Regulate the Action Potential Threshold by Modulating T-type Calcium Channels in Stellate Cells of the Entorhinal Cortex, Journal of Physiology, 597(13):3363-3387.
Liu YQ, Li MH, Fan MH, Song Y, Yu HJ, Zhi XJ, Xiao K, Lai SR, Zhang JL, Jin XQ, Shang YF, Liang J*, and Huang Z* (2019) CDYL-mediated histone crotonylation regulates stress-induced depressive behaviors, Biological Psychiatry, 85(8):635-649
Yang L, Liu Y, Fan M, Zhu G, Jin H, Liang J, Liu Z, Huang Z*, Zhang L* (2019) Identification and characterization of benzo[d]oxazol-2(3H)-one derivatives as the first potent and selective small-molecule inhibitors of chromodomain protein CDYL, Eur J Med Chem., 15;182:111656
Zhang J, Chen X, Kårbø M, Zhao Y, An L, Wang R, Wang K, Huang Z* (2018) Anticonvulsant effect of dipropofol by enhancing native GABA currents in cortical neurons in mice. J Neurophysiology, 120 (3):1404-1414
Xiao K, Sun Z, Jin X, Ma W, Song Y, Lai S, Chen Q, Fan M, Zhang J, Yue W, Huang Z* (2018) ERG3 potassium channel-mediated suppression of neuronal intrinsic excitability and prevention of seizure generation in mice. Journal of Physiology, 596(19):4729-4752.
Liu YQ, Lai SR, Ma WN, Ke W, Zhang C, Liu SM, Zhang Y, Pei F, Li SY, Yi M, Shu YS, Shang YF, Liang J*, and Huang Z* (2017) CDYL suppresses epileptogenesis through repression of axonal Nav1.6 sodium channel expression. Nature Communications, 8(1):355.
Huang Z, Li G, Aguado C, Lujan R, Shah MM. (2016) HCN1 channels reduce the rate of exocytosis from a subset of cortical synaptic terminals. Scientific Reports 7:40257.
Sun ZM and Huang Z* (2015) Progress in Research of Hyperpolarization-activated Cation Non-selective Channels and Antiepileptic Drugs Targeting the Channels. Progress in Pharmaceutical Science, 39(2): 98-104. (Invited review)
Huang Z* and Gibb A.J.* (2014) Mg2+ block properties of NMDA receptors in neonatal rat substantia nigra pars compacta dopaminergic neurones. Journal of Physiology, 592(10): 2059-78.
Huang Z, Lujan R, Kadurin I, Uebele VN, Renger JJ, Dolphin AC, Shah MM. (2011) Presynaptic HCN1 channels regulate Ca(V)3.2 activity and neurotransmission at select cortical synapses, Nature Neuroscience, 14(4):478-86
Huang Z, Lujan R, Martinez-Hernandez J, Lewis AS, Chetkovich DM, Shah MM. (2012) TRIP8b-Independent Trafficking and Plasticity of Adult Cortical Presynaptic HCN1 Channels. Journal of Neuroscience, 32(42):14835-48.
Huang Z, Walker MC, Shah MM. (2009) Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis, Journal of Neuroscience, 29(35):10979-88.
Huang Z, Wang Q, Wang JY (2003) RP-HPLC Method for Determination of Propofol in Human Serum, The Chinese Journal of Clinical Pharmacology, 19: 293-296