Professor Mark Boyett
Professor of Electrocardiophysiology
- Email: Mark.Boyett@manchester.ac.uk
- Telephone: +44 (0)161 275 1192
Research
Mark Boyett’s research focuses on the “ion channels” of the heart. The heartbeat is initiated by electrical impulses radiating in a coordinated and rhythmic manner from the pacemaker of the heart, the sinoatrial node. The electrical impulses are generated by electrically charged ions (such as sodium, calcium and potassium ions) as they flow across the cell membrane surrounding every cell in the heart via “ion channels”.
When the electrical impulses are no longer coordinated, because for example there is a fault with one of the ion channels, the result is a cardiac arrhythmia and this can result in sudden cardiac death. There are probably more than 50 types of ion channels in the heart and Mark’s group are studying (using electrophysiology, immunohistochemistry and in situ hybridisation) which ones are present in the pacemaker. They are also studying the structure of the pacemaker and using E-science they are combining the ion channel and structural data to generate a “virtual pacemaker”, in other words a highly detailed computer model of the pacemaker.
This model can be used to study diseases such as sick sinus syndrome and develop new treatments. The group are also studying how the ion channels of the pacemaker work, because it is often naturally-occurring mutations in the ion channels in the heart that result in inheritable diseases such as sick sinus syndrome. For this, they study how mutations that they make in the ion channels alter the functioning of the ion channels. They are also making atomic-resolution models of the ion channels.
When the electrical impulses are no longer coordinated, because for example there is a fault with one of the ion channels, the result is a cardiac arrhythmia and this can result in sudden cardiac death. There are probably more than 50 types of ion channels in the heart and Mark’s group are studying (using electrophysiology, immunohistochemistry and in situ hybridisation) which ones are present in the pacemaker. They are also studying the structure of the pacemaker and using E-science they are combining the ion channel and structural data to generate a “virtual pacemaker”, in other words a highly detailed computer model of the pacemaker.
This model can be used to study diseases such as sick sinus syndrome and develop new treatments. The group are also studying how the ion channels of the pacemaker work, because it is often naturally-occurring mutations in the ion channels in the heart that result in inheritable diseases such as sick sinus syndrome. For this, they study how mutations that they make in the ion channels alter the functioning of the ion channels. They are also making atomic-resolution models of the ion channels.
Biography
Mark Boyett obtained a B.Sc. in Biological Sciences (first class honours) and a Ph.D. in Physiology. For 27 years he was a Professor of Physiology at the University of Leeds and in 2005 he moved to the University of Manchester as a Professor of Cardiac Electrophysiology.
Mark’s work focuses on the ion channels in the heart that are responsible for initiating and coordinating the heart beat. His principal achievement has been to understand how the pacemaker of the heart, the sinoatrial node, works and he is frequently invited to talk about this throughout the world to both scientist and clinicians. As part of this work, Mark’s group have investigated the structure of the pacemaker from the level of the whole heart down to the individual molecule.
Mark’s work focuses on the ion channels in the heart that are responsible for initiating and coordinating the heart beat. His principal achievement has been to understand how the pacemaker of the heart, the sinoatrial node, works and he is frequently invited to talk about this throughout the world to both scientist and clinicians. As part of this work, Mark’s group have investigated the structure of the pacemaker from the level of the whole heart down to the individual molecule.
Publications
2011
- Allah EA, Tellez JO, Yanni J, Nelson T, Monfredi O, Boyett MR, Dobrzynski H. (2011). Changes in the expression of ion channels, connexins and Ca2+-handling proteins in the sino-atrial node during postnatal development. Experimental Physiology, 96(4), 426-438. eScholarID:127685
- Aslanidi OV, Colman MA, Scott J, Dobrzynski H, Boyett MR, Holden AV, Zhang H. (In-press). 3D virtual human atria: A computational platform for studying clinical atrial fibrillation. Progress in Biophysics and Molecular Biology, eScholarID:127674
- Atkinson A, Inada S, Li J, Tellez JO, Yanni J, Sleiman RN, Anderson RH, Zhang H, Boyett MR, Dobrzynksi H. (In-press). Anatomical and molecular mapping of the left and right ventricular His-Purkinje networks. Journal of Molecular and Cellular Cardiology, eScholarID:127677
- Chandler NJ, Aslanidi O, Buckley DL, Inada S, Birchall S, Molenaar P, Lei J, Anderson RH, Sharma V, Sigg D, Zhang H, Boyett MR, Dobrzynski H. (2011). A new twist in the origin of the heartbeat. Anatomical Record, eScholarID:127684
- D'Souza A, Howarth FC, Yanni J, Dobryznski H, Boyett MR, Adeghate E, Bidasee KR, Singh J. (In-press). Left Ventricle Structural Remodelling in the Prediabetic Goto-Kakizaki Rat. Experimental Physiology, eScholarID:127687
- Greener ID, Chandler NJ, Atkinson A, Tellez JO, Inada S, Molenaar P, Sharma V, Sigg D, Boyett MR, Dobrzynski H. (In-press). Molecular architecture of the human atrioventricular junction. Journal of Molecular and Cellular Cardiology, eScholarID:127683
- Greener ID, Monfredi O, Inada S, Chandler NJ, Tellez JO, Atkinson A, Taube MA, Billeter R, Anderson RH, Efimov IR, Molenaar P, Sigg DC, Sharma V, Boyett MR, Dobrzynski H. (2011). Molecular architecture of the human atrioventricular junction. Journal of Molecular and Cellular Cardiology, 50, 642-651. eScholarID:127680 | DOI:10.1016/j.yjmcc.2010.12.017
- Hao ZX, Zhang X, Nirmalan M, Davies L, Dobrzynski H, Wang X, Grace AA, Zhang H, Boyett MR, Huang CL-H, Lei M. (In-press). TGF-β1 mediated fibrosis and ion channel remodeling are key mechanisms producing sinus node dysfunction associated with SCN5A deficiency and aging. Circulation: Arrhythmia and Electrophysiology, eScholarID:127678
- Tellez J, Maczewski M, Yanni J, Sutyagin P, Mackiewicz U, Atkinson A, Inada S, Beresewicz A, Billeter R, Dobrzynski H, Boyett MR. (In-press). Ageing-Dependent Remodelling of Ion Channel and Ca2+ Clock Genes UnderlyingSinoatrial Node Pacemaking. Experimental Physiology, eScholarID:127686
- Yanni J, Tellez JO, Maczewski M, Mackiewicz U, Beresewicz A, Billeter R, Dobrzynski H, Boyett MR. (2011). Changes in ion channel gene expression underlying heart failure-induced sinoatrial node dysfunction. Circulation, Epub, eScholarID:127612 | DOI:10.1161/​CIRCHEARTFAILURE.110.957647
- Zi M, Kimura TE, Liu W, Jin J, Higham J, Kharche S, Hao G, Shi Y, Shen W, Prehar S, Mironov A, Neyses L, Bierhuizen MF, Boyett MR, Zhang H, Lei M, Cartwright EJ, Wang X. (2011). Mitogen-activated protein kinase kinase 4 deficiency in cardiomyocytes causes connexin 43 reduction and couples hypertrophic signals to ventricular arrhythmogenesis. The Journal of Biological Chemistry, 286(20), 17821-17830. eScholarID:127688 | DOI:10.1074/jbc.M111.228791
2010
- Dobrzynski H., Mofredi O, Greener ID, Atkinson A, Inada S, Taube M-A, Yanni J, Fedorenko O, Anderson RH, Efimov IR & Boyett MR. (2010). Molecular basis of the electrical activity of the atrioventricular junction and Purkinje fibres. In Tripathi, O.N., Ravens, U., & Sanguinetti, M.C (Ed.), Heart Rate and Rhythm: Molecular Basis, Pharmacological Modulation and Clinical Implications. eScholarID:127664
- Morris GM, Boyett MR, Billeter R, Dobrzynski H. (2010). Detection and measurement of cardiac ion channels. In Daniel S. Sigg, Paul Iaizzo, Yon-Fu Xiao, and Bin He (Ed.), Cardiac Electrophysiology: a primer for scientists, engineers, and clinicians. eScholarID:127666
- Aslanidi OV, Sleiman RN, Boyett MR, Hancox JC & Zhang H. (2010). Ionic mechanisms for electrical heterogeneity between rabbit Purkinje fiber and ventricular cells. Biophysical Journal, 98, 2420-2431. eScholarID:127667 | DOI:10.1016/j.bpj.2010.02.033
- Butters TD, Aslanidi OV, Inada S, Boyett MR, Hancox JC, Lei M, Zhang H. (2010). ). Mechanistic links between Na+ channel (SCN5A) mutations and impaired cardiac pacemaking in sick sinus syndrome. Ciruclation Research, 107, 126-137. eScholarID:127662 | DOI:10.1161/CIRCRESAHA.110.219949
- Monfredi OJ, Dobrzynski H, Mondal T, Boyett MR, Morris GL. (2010). Tha anatomy and physiology of the sinoatrial node - a contemporary review. Pacing and Clinical Electrophysiology, 33, 1392-1406. eScholarID:127655 | DOI:10.1111/j.1540-8159.2010.02838.x
- Xiao Y-F, Chandler NJ, Dobrzynksi H, Richardson ES, Tenbroek EM, Wilhelm JJ, Sharma V, Varghese A, Boyett MR, Iaizzo PA, Sigg DC. (2010). Hysteresis in human HCN4 channels: a crucial feature potentially affecting sinoatrial node pacemaking. Acta Physiologica Sinica, 62, 1-13. eScholarID:127670
- Yanni J, Tellez JO, Sutyagin PV, Boyett MR, Dobrzynski H. (2010). Structural remodelling of the sinoatrial node in obese old rats. Journal of Molecular and Cellular Cardiology, 48, 653-662. eScholarID:127671 | DOI:10.1016/j.yjmcc.2009.08.023
2009
- Boyett MR, Tellez JO, Dobrzynski H. (2009). The sinoatrial node - its complex structure and unique ion channel gene programme. In: Cardiac Electrophysiology: From Cell to Bedside, edited by D P Zipes and J Jalife. Elsevier Science. eScholarID:3d548
- Aslanidi O, Boyett MR, Dobrzynski H, Li J, Zhang H. (2009). Mechanisms of transition from normal to reentrant electrical activity in a model of rabbit atrial tissue: interaction of tissue heterogeneity and anisotropy. Biophys J, 96( 3), eScholarID:1d21123 | DOI:10.1016/j.bpj.2008.09.057
- Boyett, M (2009). 'And the beat goes on.' The cardiac conduction system: the wiring system of the heart. Exp Physiol, 94(10), 1035-49. eScholarID:133804 | PMID:19592411 | DOI:10.1113/expphysiol.2009.046920
- Brioschi, C, Micheloni, S, Tellez, JO, Pisoni, G, Longhi, R, Moroni, P, Billeter, R, Barbuti, A, Dobrzynski, H, Boyett, MR, DiFrancesco, D, Baruscotti, M. (2009). Distribution of the pacemaker HCN4 channel mRNA and protein in the rabbit sinoatrial node. J Mol Cell Cardiol, 47( 2), eScholarID:1d21136 | DOI:10.1016/j.yjmcc.2009.04.009
- Chandler, N, Greener, IID, Tellez, JO, Inada, S, Musa, HH, Molenaar, P, Difrancesco, D, Baruscotti, M, Longhi, R, Anderson, RR, Billeter, R, Sharma, V, Sigg, D, Boyett, MR, Dobrzynski, H. (2009). Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation, 119( 12), eScholarID:1d21134 | DOI:10.1161/CIRCULATIONAHA.108.804369
- Greener IID, Tellez JO, Dobrzynski H, Yamamoto M, Graham GM, Billeter R, Boyett MR. (2009). Ion channel transcript expression at the rabbit atrioventricular conduction axis. Circulation: Arrhythmia and Electrophysiology, 2, eScholarID:1d21164
- Inada S, Boyett MR, Dobrzynski H. (2009). Mathematical models of human sinus and atrioventricular node action potentials. Computers in Cardiology, 36, 77-80. eScholarID:127645
- Inada S, Hancox JC, Zhang H, Boyett Mr. (2009). One-dimensional mathematical model of the atrioventricular node including atrio-nodal, nodal, and nodal-his cells. Biophysical Journal, 97, 2117-2127. eScholarID:127642 | DOI:10.1016/j.bpj.2009.06.056
- Li J, Inada S, Dobrzynski H, Zhang H, Boyett MR. (2009). A modified Fitzhugh-Nagumo model that allows control of action potential duration and refractory period. Computers in Cardiology, 36, 65-68. eScholarID:127647
- Mackiewicz U, Maczewski M, Konior A, Tellez J, Nowis D, Dobrzynski H, Boyett MR, Lewartowski B. (2009). Sarcolemmal Ca2+-ATPase ability to transport Ca2+ gradually diminishes after myocardial infarction in the rat. Cardiovasc Res, 81( 3), eScholarID:1d21116 | DOI:10.1093/cvr/cvn285
- Morris GM, Boyett MR. (2009). Perspectives - biological pacing, a clinical reality. Ther Adv Cardiovasc Dis, 3, 479-483. eScholarID:127644 | DOI:10.1177/1753944709345792
- Musa, HH, Tellez, JO, Chandler, N, Greener, IID, Maczewski, M, Mackiewicz, U, Beresewicz, A, Molenaar, P, Boyett, MR, Dobrzynski, H. (2009). P2 purinergic receptor mRNA in rat and human sinoatrial node and other heart regions. Naunyn Schmiedebergs Arch Pharmacol, 379( 6), eScholarID:1d21129 | DOI:10.1007/s00210-009-0403-2
- Yanni J, Boyett MR, Anderson RR, Dobrzynski H. (2009). The extent of the specialized atrioventricular ring tissues. Heart Rhythm, 6( 5), eScholarID:1d21135 | DOI:10.1016/j.hrthm.2009.01.021
2008
- Howarth, F, Chandler, N, Kharche, S, Tellez, JO, Greener, IID, Yamanushi, T, Billeter, R, Boyett, MR, Zhang, Henggui, Dobrzynski, H. (2008). Effects of streptozotocin-induced diabetes on connexin43 mRNA and protein expression in ventricular muscle. Mol Cell Biochem, 319( 1-2), eScholarID:1d21109 | DOI:10.1007/s11010-008-9883-5
- Liu JJ, Noble P, Xiao G, Abdelrahman M, Dobrzynski H, Boyett MR, Lei M, Noble D. (2008). Role of pacemaking current in cardiac nodes: insights from a comparative study of sinoatrial node and atrioventricular node. Prog Biophys Mol Biol, 96:, 294-304. eScholarID:1d21104 | DOI:10.1016/j.pbiomolbio.2007.07.009
- Nikmaram M, Liu Jizhong, Abdelrahman M, Dobrzynski H, Boyett MR, Lei M. (2008). Characterization of the effects of ryanodine, TTX, E-4031 and 4-AP on the sinoatrial and atrioventricular nodes. Prog Biophys Mol Biol, 96:, 452-64-64. eScholarID:1d21103 | DOI:10.1016/j.pbiomolbio.2007.07.003
2007
- Boyett MR, Dobrzynski H. (2007). The sinoatrial node is still setting the pace 100 years after its discovery. Circ Res, 100( 11), eScholarID:1d21102 | DOI:10.1161/CIRCRESAHA.107.101101
- Dobrzynski H, Boyett MR, Anderson RH. (2007). New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation, 115, 1921-1932. eScholarID:127648
- Dobrzynski H, Boyett MR, Anderson RH. (2007). New insights into Sick Sinus Syndrome. Circulation, 115, 1921-1932. eScholarID:1d27437
- Jones SA, Boyett MR, Lancaster MK. (2007). Declining into failure: the age-dependent loss of the L-type calcium channel within the sinoatrial node. Ciruclation, 115, 1183-1190. eScholarID:127651
- Li J, Dobrzynski H, Abdelrahman M, Boyett MR, Lei M. (2007). Organisation of the mouse sinoatrial node: structure and expression of HCN channels. Cardiovascular Research, 73, eScholarID:1d26556 | DOI:10.1016/j.cardiores.2006.11.016
- Liu B, Westhead DR, Boyett MR, Warwicker J. (2007). Modelling the pH-dependent properties of Kv1 potassium channels. Journal of Molecular Biology, 368, 328-335. eScholarID:127652
- Yamanushi TT, Shui Z, Leach RN, Dobrzynski H, Claydon TW, Boyett MR. (2007). Role of internalisation of M2 muscarinic receptor via clathrin-coated vesicles in desensitization of the muscarinic K+ current in heart. American Journal of Physiology, 292, H1737-H1746. eScholarID:127654
- Zhang H, Zhao Y, Lei M, Dobrzynski H, Liu J, Holden A, Boyett MR. (2007). Computational evaluation of the roles of Na+ current, iNa, and cell death in cardiac pacemaking and driving. Am J Physiol Heart Circ Physiol, 292( 1), eScholarID:1d21186 | DOI:10.1152/ajpheart.01101.2005
- Boyett MR, Honjo H, Kodama I, Lancaster M, Lei M, Musa HH, Zhang Henggui. (2007). The sinoatrial node: cell size does matter. Circ Res, 101:, e81-2. eScholarID:17d991 | DOI:10.1161/CIRCRESAHA.107.161190
2006
- Boyett, MR, Inada, S, Yoo, S, Li, J, Liu, J, Tellez, JO, Greener, ID, Honjo, H, Billeter, R, Lei, M, Zhang, H, Efimov, IR, Dobrzynski, H. (2006). Connexins in the sinoatrial and atrioventricular nodes. Book Chapter. ( 42, ). eScholarID:3d857
- Barnes, K, Dobrzynski, H, Foppolo, S, Beal, PR, Ismat, F, Scullion, ER, Sun, L, Tellez, JO, Ritzel, MW, Claycomb, WC, Cass, CE, Young, JD, Billeter-Clark, R, Boyett, MR, Baldwin, SA. (2006). Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circulation Research, 99(5), eScholarID:1d27348
- Dobrzynski H, Billeter R, Greener ID, Tellez JO, Chandler NJ, Flagg TP, Nichols, Lopatin AN, Boyett MR. (2006). Expression of Kir2.1 and Kir6.2 transgenes under the control of the alpha-MHC promoter in the sinoatrial and atrioventricular nodes in transgenic mice. Journal of Molecular and Cellular Cardiology, 41(5), eScholarID:1d27351
- Makary SY, Claydon TW, Dibb KKM, Boyett MR. (2006). Base of pore loop is important for rectification, activation, permeation and block of Kir3.1/Kir3.4. Biophysical J, 90, 4018-4034. eScholarID:1d27103
- Tellez JO, Dobrzynski H, Greener ID, Graham GM, Laing E, Honjo H, Hubbard SJ, Boyett MR, Billetter R. (2006). Differential Expression of Ion Channel Transcripts in Atrial Muscle and Sinoatrial Node in Rabbit. Circulation Research, eScholarID:1d27354
- Yamamoto M, Dobrzynski H, Tellez JO, Niwa R, Billeter R, Honjo H, Kodama I, Boyett MR. (2006). Extended atrial conduction system characterized by the expression of the HCN4 channel and connexin45. Cardiovascular Research, eScholarID:1d27438
- Yamanushi TT, Shui Z, Leach RN, Dobrzynski H, Claydon TW, Boyett MR. (2006). Role of internalisation of M2 muscarinic receptor via clathrin-coated vesicles in desensitization of the muscarinic K+ current in heart. American Journal of Physiology - Heart and Circulatory Physiology, eScholarID:1d27353
- Yoo, S, Dobrzynski, H, Fedorov, VV, Xu, SZ, Yamanushi, TT, Jones, SA, Yamamoto, M, Nikolski, VP, Efimov, IR, Boyett, MR. (2006). Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat. Circulation, 114(13), 1360-71. eScholarID:1d27350 | DOI:10.1161/CIRCULATIONAHA.106.613182
2005
- Makary SY, Clayton TW, Enkvetchakul D, Nichols CG, Boyett MR. (2005). A difference in inward rectification and polyamine block and permeation between the Kir2.1 and Kir3.1/Kir3.4 K+ channels. Journal of Physiology, 568, 749-766. eScholarID:1d26769
2004
- Jones SA, Lancaster MK, Boyett MR. (2004). Ageing-related changes of connexins and conduction within the sinoatrial node. Journal of Physiology, 560, 429-437. eScholarID:1d26770
- Lancaster MK, Jones SA, Harrison SM, Boyett MR. (2004). Intracellular Ca2+ and pacemaking within the rabbit sinoatrial node: heterogeneity of role and control. J. Physiol, 556, 481-494. eScholarID:1d26771
2003
- Honjo, H, Inada, S, Lancaster, MK, Yamamoto, M, Niwa, R, Jones, SA, Shibata, N, Mitsui, K, Horiuchi, T, Kamiyi, K, Kodama, I, Boyett, MR. (2003). Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity. Circulation Research, 92, e41-e44. eScholarID:1d26591 | DOI:10.1161/01.RES.0000055904.21974.BE
2001
- Shui Z, Khan IN, Haga T, Benovic JL, Boyett MR. (2001). Control of the cardiac muscarinic K+ channel by B-arrestin 2. Journal of Biological Chemistry, 276, 11691-11697. eScholarID:1d26789 | DOI:10.1074/jbc.M011007200
- Zhang H, Holden AV, Boyett MR. (2001). Gradient model versus mosaic model of the sinoatrial node. Circulation, 103, 584-588. eScholarID:1d26266