The autonomic nervous system continuosly adjusts cardiac activity to the needs of the body in the different environmental conditions, from rest to acute stresses.
i) How do sympathetic neurons communicate to cardiac cells to achieve flexible and reliable control over heart function?
ii) How does intercellular communication operate in diseases characterized (e.g. Heart Failure, Myocardial Infarction) dysfunction of the neurogenic control of the heart?

The lab is devoted to improving basic understanding of cardiac cell biology and the mechanisms of neurogenic regulation of cardiac function. In particular we focus on the biophysics of intercellular communication between autonomic neurons and cardioimyocytes, and how alterations in this process may underlie stress-dependent arryhthmias and heart failure. The lab employs techniques ranging from molecular and cell biology, to advanced fluorescence based measurements of second messenger dynamics, to optogenetics.

Group Members
Key Publications

The sympathetic nervous system is an important physiologic modulator of the heart. Sympathetic neurons play a critical role in matching cardiac function with the acute variation of perfusional requests, as those associated to changes in somatic activity or emotions; in addition, they adapt myocardial structure to states of chronically elevated workload, such as hypertension or valvular diseases.
Extensive research has led to the common tenet that sympathetic innervation controls cardiac function and structure by releasing neurotransmitters (mainly noradrenaline) into the heart interstitium, causing activation of adrenergic receptors in the target cells.
We have previously demonstrated that the myocardial sympathetic network is highly organized and the neuro-cardiac interaction is underain by multiple interaction sites bringing neurons at very narrow intercellular distance with the target cardiomyocyte membrane. Based on this finding, our research aim is to understand the biophysics of neuro-cardiac communication in the physiological heart and in diseases associated to dysfunctional autonomic cardiac innervation.
A well determined condition leading to the development of arrhythmia in structrurally intact hearts is unbalanced activation of the sympathetic neurons in different regions of the heart. We aim to test whether dysregulation of neuro-effector mechanisms may feature in common genetic arrhythmia syndromes, e.g. Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT).

Physiology and cell biophysics of the intercellular communication between sympathetic neurons and the heart.

Intercellular communication between the sympathetic nervous system (SNS) and the heart underlies the most important extrinsic regulation of heart function. Cardiac sympathetic stimulation is engaged at the greatest degree during acute stresses, commonly associated to the so-called ‘fight-or-flight' response (Jansen et al., 1995). At the same time, SNs continuously tune heart rhythm, contributing to the non-random variation of the beat-to-beat intervals, referred to as physiological ‘heart rate variability’ (Lombardi et al., 1996). To comply with such a wide effect range, neurons must deliver their signals to CMs rapidly (for precise control of cardiac responses), efficiently (to minimize neurotransmitter disposal) and, if needed, potently (to maximize heart pumping). Neurotransmission based on direct coupling, similar to that occurring in neuromuscular junctions (NMJ) (Slater, 2003), would fulfill all these requirements. Such mode of communication has previously been proposed, mostly based on indirect morphologic and in vitro data, by a narrow group of research papers (Choate et al., 1993; Hirst et al., 1996), but it has not been addressed in the intact innervated heart. The aim of our research is to understand the molecular determinants of neuro-cardiac interaction, and the dynamics of intercellular signaling between the neurons and their target myocardial cells.

Disease mechanism in Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by stress induced ventricular tachyarrhythmias leading to syncope and sudden cardiac death. The clinical presentation includes exercise- or emotion-induced syncopal events and a distinctive pattern of reproducible, stress-related, bidirectional VT in the absence of either structural heart disease and of prolonged QT interval. Two genetic variants of CPVT have been identified, one transmitted as an autosomal dominant trait caused by mutations in the gene encoding the RyR2 and one recessive form caused by mutations in the cardiac-specific isoform of the CASQ2.

An unresolved question bearing critical consequences on the therapeutic perspectives in CPVT concerns the role of the sympathetic stimulation in triggering the stress induced arrhythmias.
There is general consensus that the ventricular tachyarrhythmias in CPVT are triggered by a sudden increase in sympathetic activity, and the rationale for anti-adrenergic therapy with β-blockers is based on this observation. As an alternative to chronic pharmacological treatment, surgical sympathetic denervation has been successfully used in several trials. Regional differences in sympathetic discharge have been suggested to cause ventricular arrhythmias. However, the mechanisms of regional control over cardiac activity by specific groups of cardiac sympathetic terminals is largely unexplored in both physiological and pathophysiological states. Given the role sympathetic activation has in triggering life threatening events in CPVT, it is of paramount importance to understand whether specific cardiac structures are the critical target of sympathetic discharge. We are using optogenetics to directly assess the effect of regional sympathetic innervation on cardiac function and electrophysiology.

The aim of our research is to identify the conditions favoring arrhythmia formation and triggering, to uncover potentially new therapeutic strategies and pharmacological targets to treat CPVT.

Antonio Campo


Lolita Dokshokova


  1. Zaglia T, Ceriotti P, Campo A, Borile G, Armani A, Carullo P, Prando V, Coppini R, Vida V, Stølen TO, Ulrik W, Cerbai E, Stellin G, Faggian G, De Stefani D, Sandri M, Rizzuto R, Di Lisa F, Pozzan T, Catalucci D, and Mongillo M. Content of the Mitochondrial Calcium Uniporter (MCU) in cardiomyocytes is regulated by microRNA-1 in physiologic and pathologic hypertrophy. PNAS 2017 Oct 9 (in the press)
  2. Zaglia T, Mongillo M. Cardiac sympathetic innervation, from a different point of (re)view. J Physiol. 2017 Jun 15;595(12):3919-3930. doi: 10.1113/JP273120.
  3. Pianca N, Zaglia T, Mongillo M. Will cardiac optogenetics find the way through the obscure angles of heart physiology? Biochem Biophys Res Commun. 2017 Jan 22;482(4):515-523. doi: 10.1016/j.bbrc.2016.11.104.
  4. Franzoso M, Zaglia T, Mongillo M. Putting together the clues of the everlasting neuro-cardiac liaison. Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1904-15. doi: 10.1016/j.bbamcr.2016.01.009. Epub 2016 Jan 14. Review.
  5. Zaglia T, Pianca N, Borile G, Da Broi F, Richter C, Campione M, Lehnart SE, Luther S, Corrado D, Miquerol L, Mongillo M. Optogenetic determination of the myocardial requirements for extrasystoles by cell type specific targeting of Channelrhodopsin-2. PNAS 2015 Aug 11;112(32):E4495-504. doi: 10.1073/pnas.1509380112. Epub 2015 Jul 23
  6. Borile G, de Mauro C, Urbani A, Alfieri D, Pavone FS, Mongillo M. Multispot multiphoton Ca²⁺ imaging in acute myocardial slices. J Biomed Opt. 2015 May;20(5):51016. doi: 10.1117/1.JBO.20.5.051016.
  7. Zaglia T, Milan G, Franzoso M, Bertaggia E, Pianca N, Piasentini E, Voltarelli VA, Chiavegato D, Brum PC, Glass DJ, Schiaffino S, Sandri M, Mongillo M. Cardiac sympathetic neurons provide trophic signal to the heart via β2-adrenoceptor-dependent regulation of proteolysis. Cardiovasc Res. 2013 Feb 1;97(2):240-50. doi: 10.1093/cvr/cvs320.
  8. Plazzo AP, De Franceschi N, Da Broi F, Zonta F, Sanasi MF, Filippini F, Mongillo M. Bioinformatic and mutational analysis of channelrhodopsin-2 protein cation-conducting pathway. J Biol Chem. 2012 Feb 10;287(7):4818-25. doi: 10.1074/jbc.M111.326207. Epub 2011 Dec 2.
  9. Lehnart SE*, Mongillo M*, Bellinger A, Lindegger N, Chen BX, Hsueh W, Reiken S, Wronska A, Drew LJ, Ward CW, Lederer WJ, Kass RS, Morley G, Marks AR. (*: co-first author) Leaky Ca2+ release channel/ryanodine receptor 2 causes seizures and sudden cardiac death in mice. J Clin Invest. 2008 Jun;118(6):2230-45. doi: 10.1172/JCI35346.
  10. Mongillo M, Marks AR. Models of heart failure progression: Ca2+ dysregulation. Drug Discovery Today: Disease Models - Vol. 4 - Issue 4 - 2007 - pp. 191-196


  • 2015 – present Associate Professor, Dept of Biomedical Sciences, University of Padua
  • 2009 – present PI, Venetian Institute of Molecular Medicine, Padua
  • 2008 – 2015 Researcher at the Faculty of Medicine, University of Padua
  • 2006 – 2008 Research Fellowship, Columbia University, New York
  • 2005 – 2006 Clinical Fellow, Imperial College London, UK
  • 2005 Ph.D. in Molecular and Cellular Biology and Pathology, University of Padua
  • 2001 Degree in Medicine at the University of Padua

Selected Awards

  • 2005 – Bocchetti Protti Award, Belluno, Italy
  • 2006 – Norman Alpert Award, European Society of Cardiology
  • 2016 – Guido Tarone Award, Heart Failure Association of the ESC