Development of patch clamp technology in the past 10 years: visual analysis based on CiteSpace and VOSviewer

doi:10.12307/2025.615

Abstract

Abstract: BACKGROUND: Patch clamp technique has been developed for more than 40 years as the “gold standard” for the study of ion channels. However, the research content of scientific research institutions is relatively independent, and the existing research results are not systematically summarized, which leads to the phenomenon of high repeatability and weak innovation in the existing research. Therefore, it is urgent to make a comprehensive review of patch clamp technology to clarify the current research status, hot spots, and future development direction.
OBJECTIVE: To summarize the research status and development trend of patch clamp technique in recent 10 years.
METHODS: Publications on patch clamp technology from 2013 to 2023 were collected using the Web of Science core collection database. CiteSpace and VOSviewer software were used to quantify the number of publications and analyze the network of literature entries, including countries, institutions, journals, authors, keywords, highly cited literature, and co-cited references.
RESULTS AND CONCLUSION: (1) In recent 10 years, the research in the field of patch clamp technology has gradually entered a stage of stable development. (2) China and the United States are the leading countries in this regard. The Chinese Academy of Sciences is an institution with core influence. Journal of Neuroscience is the main publication. Park, Won Sun team (Jeonbuk National University) and Chu, Li team (Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease) have made outstanding contributions in this field, but there is less collaboration and communication between the teams and no network cooperation model has been formed. (3) Patch clamp technology is mainly used in the electrophysiological characteristics of the nervous system and the pathological mechanism of the disease, which is the focus of researchers’ continuous attention. (4) In the study of electrophysiological characteristics of cardiovascular system and its pathological mechanism, the electrophysiological characteristics of primary cardiomyocytes and induced pluripotent stem cell-derived cardiomyocytes and the pathological mechanism of atrial fibrillation, cardiotoxicity, sudden cardiac death, hypertension and other cardiovascular diseases have been the focus of research in recent years. (5) In the application of patch clamp technology combined with other biotechnology, it will be an important research direction to focus on the cross fusion with optogenetics, two-photon calcium imaging and other technologies. (6) In the research of drug screening and identification of therapeutic targets, especially the research of patch clamp technology and traditional Chinese medicine compound, it will become a great help in the future research of component traditional Chinese medicine.

Key words: ">patch clamp technique, whole cell recording, bibliometrics, CiteSpace, VOSviewer, visual analysis, neuroscience, electrophysiology, pathological mechanism, ion channel

CLC Number:

Guo Haizhen, Cong Zidong, Zhao Yuke, Li Xiaofeng, Yu Lu, Qian Shule, Wang Runying, Du Wuxun. Development of patch clamp technology in the past 10 years: visual analysis based on CiteSpace and VOSviewer[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(31): 6717-6726.

Figures/Tables 3

2.1 年度发文趋势结果通过对膜片钳技术的相关文献进行年度发表文献趋势可视化分析，见图1。可以发现，近10年膜片钳技术的相关研究发文量虽呈波动下降趋势，但较前并未出现骤减情况，表明该领域研究热度虽然有所下降，但整体发展态势稳定。 2.2 作者可视化结果膜片钳技术研究领域文献共有14 120个作者。根据普赖斯定律的核心作者的计算公式[17]，计算出核心作者中的最低发文量M≈3.745，约为4篇。因此，统计出发文量≥4篇核心作者共587位。其中，发文量≥10篇的核心作者有52位，见图2。统计结果显示：在膜片钳技术研究领域并未形成显著的核心作者群，但核心作者之间形成了稳定的合作团队。Park，Won Sun团队(韩国全北国立大学)、Chu，Li团队(中国河北省心脑血管病中医药防治研究重点实验室)、Ackerman，Michael J.团队(美国明尼苏达州罗切斯特市梅奥诊所)和Hahn，Sang June团队(韩国加图立大学)是4个较大且相对稳定的学术团队。作者发文量排名前5名的分别为Jang，Il-Sung(25篇，韩国庆北大学)、Park，Won Sun(23篇，韩国江原国立大学)、Hahn，Sang June(21篇，韩国加图立大学)、Han，Seong Kyu(21篇，韩国全北国立大学)和Bae，Young Min(17篇，韩国江原国立大学)。 2.3 机构可视化结果对膜片钳技术研究领域文献中所涉及的机构进行统计，共涉及2 465个机构。其中，发文量≥15篇共76个机构，见图3。结果显示：在膜片钳技术研究领域涉及的机构较多，机构之间具有密切的联系。其中，Chinese Acad Sci(中国科学院，中国，连接数16)是与其他机构联系最广泛的机构，具有较大的影响力，其次是Chinese Acad Med Sci(中国医学科学院，连接数13)、Wuhan Univ(武汉大学，连接数12)、Fudan Univ(复旦大学，连接数11)和Nanjing Med Univ(南京医科大学，连接数11)。发文量频次排名前5位的机构是Fudan Univ(61篇)、Harbin Med Univ (哈尔滨医科大学，57篇)、Chinese Acad Sci(46篇)、Huazhong Univ Sci & Technol(华中科技大学， 40篇)、Russian Acad Sci(俄罗斯科学院，37篇)。 2.4 国家可视化结果 2013-2023年全球共涉及77个国家发表了膜片钳技术相关文献。其中，发文量≥7篇有42个国家。如图4所示。统计结果显示：在膜片钳技术的研究，各国之间均有不同程度的联系。其中美国(连接数39)是与其他国家联系最广泛的国家，其次是德国(连接数35)、英格兰(连接数31)、法国(连接数27)和中国(连接数23)。发文量中国(911篇)排名第一，拥有超过900份出版物(占总数的29.87%)，紧随之后的是美国(882篇)、日本(305篇)、德国(298篇)和韩国(191篇)。 2.5 期刊可视化结果对膜片钳技术研究领域文献的出版期刊进行统计，共涉及638家期刊。其中，发文量≥12篇有55家期刊，见图5。统计结果显示：对于膜片钳技术的研究，期刊之间联系密切，研究内容涉及神经科学、药理学、生理学、分子生物学、细胞生物学等多个学科。《Journal of Neuroscience》(连接数25)是与其他期刊合作最广泛的期刊，具有较大的影响力，其次是《European Journal of Pharmacology 》(连接数24)、《Journal of Neurophysiology(神经生理学杂志)》(连接数23)、《International Journal of Molecular Sciences》(连接数21)和《Plos One(公共科学图书馆?综合)》(连接数21)。从发文量来看，《Journal of Neuroscience》(130篇)遥遥领先；其次是《Plos One》(86篇)、《European Journal of Pharmacology》(75篇)、《Journal of Neurophysiology》(75篇)和《International Journal of Molecular Sciences》(58篇)。 2.6 高被引文献结果对膜片钳技术研究领域文献进行统计，共有3 050篇文章。其中，被引频次≥50次有171篇，如图6所示。统计结果显示：被引频次排名第一的Jiang (2015)高达503次，其次为Talantova (2013)、Polack (2013)、Cork (2015)和Ko(2013)[18-22]，详见表1。 "

2.8.2 关键词聚类和时区演化结果关键词聚类分析是将文献中具有相似内涵的关键词词群进行归类总结分析，以协助研究者快速掌握该领域研究的方向[28]。在Citespace软件中，选用对数似然算法对关键词进行聚类分析，见图9。统计结果显示：在膜片钳技术的研究领域，共形成了7个关键词聚类标签，图谱中Modularity值为0.359 2 > 0.3，Mean Silhouette值为0.666 8 > 0.5，表明此次聚类为高效的[29]。聚类#0(interneuron，中间神经元)的内容多集中采用膜片钳技术观察各大脑区域(丘脑、前额叶皮质、杏仁核等)自发或刺激后诱发的阈下动力学变化、神经系统疾病病理机制和神经行为学调节机制；聚类#1(atrial fibrillation，心房颤动)研究的主要是心血管系统疾病的病理机制及其药物治疗的电生理特征；聚类#2 (membrane capacitance，膜电容)和#4(molecular biology，分子生物学)主要是研究各种疾病状态下细胞膜电容特性及其分子生物学机制；聚类#3 (neuropathic pain神经病理性疼痛)关注神经的抑制性调节机制，如镇痛药物对神经病理性疼痛的镇痛机制；聚类#5(bdnf，脑源性神经营养因子)主要研究中枢神经系统氨基酸、肽和蛋白质等受体的表达与释放，尤其是脑源性神经营养因子表达及其相关信号通路研究；聚类#6(anesthetics，麻醉剂)研究重点为麻醉剂作用的电生理机制。关键词时区演化是在关键词聚类的基础上进行分析，侧重于勾画聚类关键词的历史跨度，根据时间跨度说明该聚类下研究内容的发展时间以及连贯性，从而明晰发展趋势。在CiteSpace软件进行分析，选择“timeline”模块进行分析，见图10。统计结果显示：在近10年膜片钳技术领域中，聚类#0，#1，#2，#3，#4一直受到学者关注，是该领域的研究热点；而聚类#5和聚类#6的研究近年趋冷。 2.8.3 关键词突现结果突现分析是指关键词在某个时期内有较高的引用率，这可以测试一个研究领域在一定时期内是否热门以及突出新出现的热点[30-31]。如果这些出现的概率高于数据的全局阈值，则认为这些关键词为突现词，主要体现研究前沿并预测研究发展方向[32]。在CiteSpace软件中，选择“Burstness”模块进行图谱绘制，见图11。统计分析得到17个突现词，分别为：ganglion cell(神经节细胞)、central nervous system(中枢神经系统)、propofol(异丙酚)、dorsal horn neuron(背角神经元)、schizophrenia (精神分裂症)、motoneuron(运动神经元)、asthma(哮喘)、stress(应激)、electrophysiological property(电生理特性)、circuit(回路)、risk(风险)、mitochondria(线粒体)、deficiency(缺陷)、oscillation(振荡)、anxiety(焦虑)、association(联想)和parkinsons disease(帕金森病)。 "

References

[1] 黄燕云,高洁,张利娜,等.利用全细胞膜片钳技术记录大鼠脑片NMDA电流的研究[J].中国应用生理学杂志,2021, 37(5):459-462.
[2] 于婷婷,丁懿宁,阎美卉,等.基于膜片钳技术的丹红注射液对人诱导多能干细胞衍生心肌细胞电生理的影响研究[J]. 药物评价研究,2024,47(5):1010-1016.
[3] BELL D C, FERMINI B. Use of automated patch clamp in cardiac safety assessment: past, present future perspectives. J Pharmacol Toxicol Methods. 2021;111: 107114.
[4] LOVISOLO D. Patch clamp: the first four decades of a technique that revolutionized electrophysiology and beyond. Rev Physiol Biochem Pharmacol. 2023;186:1-28.
[5] ROGERS M, OBERGRUSSBERGER A, KONDRATSKYI A, et al. Using automated patch clamp electrophysiology platforms in ion channel drug discovery: an industry perspective. Expert Opin Drug Discov. 2024; 19(5):523-535.
[6] MELGARI D, CALAMAIO S, FROSIO A, et al. Automated patch-clamp and induced pluripotent stem cell-derived cardiomyocytes: a synergistic approach in the study of brugada syndrome. Int J Mol Sci. 2023;24(7):6687.
[7] NOGUCHI A, IKEGAYA Y, MATSUMOTO N. In vivo whole-cell patch-clamp methods: recent technical progress and future perspectives. Sensors (Basel). 2021;21(4): 1448.
[8] HORVATH B, SZENTANDRASSY N, DIENES C, et al. Exploring the coordination of cardiac ion channels with action potential clamp technique. Front Physiol. 2022;13:864002.
[9] GAO J, LIAO C, LIU S, et al. Nanotechnology: new opportunities for the development of patch-clamps. J Nanobiotechnology. 2021;19(1):97.
[10] LINDERS LE, SUPIOT LF, DU W, et al. Studying synaptic connectivity and strength with optogenetics and patch-clamp electrophysiology. Int J Mol Sci. 2022; 23(19):11612.
[11] JIANG F, ZHANG F, SU Y, et al. Knowledge mapping of disease-modifying therapy (DMT) in multiple sclerosis (MS): a bibliometrics analysis. Heliyon. 2024;10(11): e31744.
[12] QU F, WANG G, WEN P, et al. Knowledge mapping of immunotherapy for breast cancer: a bibliometric analysis from 2013 to 2022. Hum Vaccin Immunother. 2024;20(1):2335728.
[13] ZHANG L, LI Y, ZHANG Y, et al. Development and trends in metabolomics studies in psoriasis: a bibliometric analysis of related research from 2011 to 2024. Heliyon. 2024; 10(8):e29794.
[14] ALMUHAIDIB S, ALQAHTANI R, ALOTAIBI HF, et al. Mapping the landscape of medical research in the Arab world countries: a comprehensive bibliometric analysis. Saudi Med J. 2024;45(4):387-396.
[15] CHEN L, CHEN J, WU M, et al. Analyzing the bibliometrics of brain-gut axis and Parkinson’s disease. Front Neurol. 2024; 15:1343303.
[16] LANG X, LI L, LI Y, et al. Effect of diabetes on wound healing: a bibliometrics and visual analysis. J Multidiscip Healthc. 2024; 17:1275-1289.
[17] 张子婷,郑彦宁,袁芳.多指标核心作者识别方法研究[J].现代情报,2020,40(7): 144-151.
[18] JIANG X, SHEN S, CADWELL CR, et al. Principles of connectivity among morphologically defined cell types in adult neocortex. Science. 2015;350(6264):aac9462.
[19] TALANTOVA M, SANZ-BLASCO S, ZHANG X, et al. Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss. Proc Natl Acad Sci India Sect B Biol Sci. 2013;110(27): E2518-E2527.
[20] POLACK P, FRIEDMAN J, GOLSHANI P. Cellular mechanisms of brain state-dependent gain modulation in visual cortex. Nat Neurosci. 2013;16(9):1331-1339.
[21] CORK SC, RICHARDS JE, HOLT MK, et al. Distribution and characterisation of glucagon-like peptide-1 receptor expressing cells in the mouse brain. Mol Metab. 2015; 4(10):718-731.
[22] KO H, COSSELL L, BARAGLI C, et al. The emergence of functional microcircuits in visual cortex. Nature. 2013;496(7443):96-100.
[23] HAMILL OP, MARTY A, NEHER E, et al. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981;391(2):85-100.
[24] MARGRIE TW, BRECHT M, SAKMANN B. In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflugers Arch. 2002;444(4):491-498.
[25] NELSON MT, QUAYLE JM. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 1995;268(4 Pt 1):C799-C822.
[26] MARKRAM H, TOLEDO-RODRIGUEZ M, WANG Y, et al. Interneurons of the neocortical inhibitory system. Nat Rev Neurosci. 2004;5(10):793-807.
[27] MADISEN L, ZWINGMAN T A, SUNKIN S M, et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 2010;13(1):133-140.
[28] ZHAO ML, LU ZJ, YANG L, et al. The cardiovascular system at high altitude: a bibliometric and visualization analysis. World J Cardiol. 2024;16(4):199-214.
[29] HUO Q, LUO X, XU Z, et al. Machine learning applied to epilepsy: bibliometric and visual analysis from 2004 to 2023. Front Neurol. 2024;15:1374443.
[30] XU D, WANG Y, WANG K, et al. A scientometrics analysis and visualization of depressive disorder. Curr Neuropharmacol. 2021;19(6):766-786.
[31] YAN W, ZHENG K, WENG L, et al. Bibliometric evaluation of 2000-2019 publications on functional near-infrared spectroscopy. Neuroimage. 2020;220:117121.
[32] KIM MC, NAM S, WANG F, et al. Mapping scientific landscapes in UMLS research: a scientometric review. J Am Med Inform Assoc. 2020;27(10):1612-1624.
[33] TAO C, ZHANG G, XIONG Y, et al. Functional dissection of synaptic circuits: in vivo patch-clamp recording in neuroscience. Front Neural Circuits. 2015;9:23.
[34] SUK HJ, BOYDEN ES, van WELIE I. Advances in the automation of whole-cell patch clamp technology. J Neurosci Methods. 2019;326: 108357.
[35] PARK S, KANG M, HEO R, et al. Inhibition of voltage-dependent K+ channels by antimuscarinic drug fesoterodine in coronary arterial smooth muscle cells. Korean J Physiol Pharmacol. 2022;26(5):397-404.
[36] SEO MS, AN JR, JUNG HS, et al. Suppression of voltage-gated K+ channels by darifenacin in coronary arterial smooth muscle cells. Eur J Pharmacol. 2021;891:173707.
[37] AN JR, JUNG HS, SEO MS, et al. The effects of tegaserod, a gastrokinetic agent, on voltage-gated K+ channels in rabbit coronary arterial smooth muscle cells. Clin Exp Pharmacol Physiol. 2021;48(5):748-756.
[38] AN JR, SEO MS, JUNG HS, et al. The inhibitory effect of ziprasidone on voltage-dependent K+ channels in coronary arterial smooth muscle cells. Biochem Biophys Res Commun. 2020;529(2):191-197.
[39] ZHANG M, QI J, HE Q, et al. Liquiritigenin protects against myocardial ischemic by inhibiting oxidative stress, apoptosis, and L-type Ca2+ channels. Phytother Res. 2022;36(9):3619-3631.
[40] LI J, YANG Y, WANG H, et al. Baicalein ameliorates myocardial ischemia through reduction of oxidative stress, inflammation and apoptosis via tlr4/myd88/mapks/NF-κB pathway and regulation of Ca2+ homeostasis by l-type Ca2+ channels. Front Pharmacol. 2022;13:842723.
[41] ZHAO Z, LIU M, ZHANG Y, et al. Cardioprotective effect of monoammonium glycyrrhizinate injection against myocardial ischemic injury in vivo and in vitro: involvement of inhibiting oxidative stress and regulating Ca2+ homeostasis by L-type calcium channels. Drug Des Devel Ther. 2020;14:331-346.
[42] WU D, YU N, GAO Y, et al. Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation. Mol Neurodegener. 2023;18(1):23.
[43] TIAN T, CAI Y, QIN X, et al. Forebrain E-I balance controlled in cognition through coordinated inhibition and inhibitory transcriptome mechanism. Front Cell Neurosci. 2023;17:1114037.
[44] ZHU J, CHEN C, LI Z, et al. Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function. Neural Regen Res. 2023;18(11):2449-2458.
[45] PENG X, MAO Y, TAI Y, et al. Characterization of anxiety-like behaviors and neural circuitry following chronic moderate noise exposure in mice. Environ Health Perspect. 2023;131(10):107004.
[46] HUANG M, YANG Z, LI Y, et al. Dopamine D1/D5 receptor signaling is involved in arrhythmogenesis in the setting of takotsubo cardiomyopathy. Front Cardiovasc Med. 2021;8:777463.
[47] XU Q, HUANG X, MENG Z, et al. Antiarrhythmic effects of vernakalant in human-induced pluripotent stem cell-derived cardiomyocytes from a patient with short QT syndrome Type 1. J Cardiovasc Dev Dis. 2022;9(4):112.
[48] ZHONG R, ZHANG F, YANG Z, et al. Epigenetic mechanism of L-type calcium channel beta-subunit downregulation in short QT human induced pluripotent stem cell-derived cardiomyocytes with CACNB2 mutation. Europace. 2022;24(12):2028-2036.
[49] LIU P, YANG Y, ZHANG H, et al. The effect of TWIK-1 two pore potassium channels on cardiomyocytes in low extracellular potassium conditions. Front Biosci (Landmark Ed). 2023;28(3):51.
[50] NAGARAJA RY, STILES MA, SHERRY DM, et al. Synapse-specific defects in synaptic transmission in the cerebellum of W246G mutant ELOVL4 rats-a model of human SCA34. J Neurosci. 2023;43(33):5963-5974.
[51] CHEN YC, RINDNER DJ, FOWLER JP, et al. Extracellular ATP neurotransmission and nicotine sex-specifically modulate habenular neuronal activity in adolescence. J Neurosci. 2023;43(48):8259-8270.
[52] 韩昕,李莎莎,陈曦,等.基于CiteSpace和VOSviewer对女贞子的研究现状与热点分析[J].特产研究,2024,46(3):47-55.
[53] LIU H, FANG X, MA Q, et al. Research hotspots of polycystic ovary syndrome and hyperandrogenism from 2008 to 2022: bibliometric analysis. Gynecol Endocrinol. 2024;40(1):2326102.
[54] 贾炜姣,代广斌,耿国帅,等.膜片钳技术在细胞电生理研究方面的最新应用[J].高校化学工程学报,2018,32(4):767-778.
[55] LLANOS MA, ENRIQUE N, ESTEBAN-LOPEZ V, et al. A combined ligand- and structure-based virtual screening to identify novel NaV1.2 blockers: in vitro patch clamp validation and in vivo anticonvulsant activity. J Chem Inf Model. 2023;63(22):7083-7096.
[56] DALLAS ML, BELL D. Advances in ion channel high throughput screening: where are we in 2023? Expert Opin Drug Discov. 2024;19(3):331-337.
[57] YANG Y, LIU A, TSAI CT, et al. Cardiotoxicity drug screening based on whole-panel intracellular recording. Biosens Bioelectron. 2022;216:114617.
[58] ZHAO Q, ZHANG X, LONG S, et al. Licochalcone mediates the pain relief by targeting the voltage-gated sodium channel. Mol Pharmacol. 2023;104(4):133-143.
[59] GONG JH, ZHANG CM, WU B, et al. Central and peripheral analgesic active components of triterpenoid saponins from Stauntonia chinensis and their action mechanism. Front Pharmacol. 2023;14:1275041.
[60] ANNECCHINO LA, SCHULTZ SR. Progress in automating patch clamp cellular physiology. Brain Neurosci Adv. 2018;2: 2398212818776561.