- Discovering Padova
- Il Bo
Education and training:
1979, University of Padova, Degree (Laurea) in Chemistry, Magna cum Laude.
1979-1982, Research Fellow (Lab. Prof. G. Azzone), Institute of General Pathology, University of Padova: Energy transduction in mitochondria.
1984-1985, Postdoctoral Fellow (two EMBO Short Term Fellowships), Dept of Membrane Research (lab. Prof. R. Caplan), Weizmann Institute of Science, Israel: Non-equilibrium thermodynamics of oxidative phosphorylation and kinetic modelling of mitochondrial H+ pumps.
1987-1990, Postdoctoral Fellow (EMBO Long Term Fellowship and Fogarty International Fellowship), Dept of Cellular and Molecular Physiology (Lab Prof P. Hess), Harvard Medical School, U.S.A.: Biophysics of voltage-gated Ca2+ channels.
Employment and Research experience:
1983-1991, CNR Researcher, CNR Unit Physiology of Mitochondria, Institute of General Pathology, University of Padova: Energy transduction in mitochondria.
1991-1993, CNR Director of Research, CNR Unit Physiology of Mitochondria, Dept. of Biomedical Sciences, Univ. of Padova: Biophysics and physiology of neuronal Ca2+ channels.
1993-2000 Associate Professor of General Physiology (Faculty of Sciences), Dept. of Biomedical Sciences, Univ. of Padova: Biophysics and physiology of neuronal Ca2+ channels.
2000-present, Professor of Physiology (Faculty of Sciences), Dept. of Biomedical Sciences, Univ. of Padova (2005-present: Coordinator of the PhD program in Neurobiology within the PhD School of Biosciences and Biotechnologies): Calcium channelopathies of the central nervous system; in particular familial hemiplegic migraine; migraine pathophysiology
1985, Luigi Galvani Prize of the Bioelectrochemical Society.
1996-2000 Member of Council of the Italian Society of Pure and Applied Biophysics
1996-2002 Member of Council of IUPAB (Int. Union of Pure and Applied Biophysics)
2001, National Prize “President of the Republic” in Mathematical, Physical and Natural Sciences awarded by the Accademia dei Lincei
2010-present Member of Faculty of 1000
2011-present Member of the Venetian Institute of Letters, Arts and Sciences
FHM type 1 mutations produce gain-of-function of human recombinant CaV2.1 calcium channels (Hans et al, 1999 J Neurosci; Tottene et al, 2002 Proc Nat Acad Sci; Tottene et al, 2005 J Biol Chem).
Gain-of-function of neuronal Ca2.1 channels in knockin mice carrying FHM type 1 mutations and loss-of-function of astrocytic α2 Na/K ATPases in knockin mice carrying a FHM type 2 mutation both lead to facilitation of induction and propagation of cortical spreading depression (CSD), the phenomenon underlying migraine aura (van den Maagdenberg et al, 2004 Neuron; van den Maagdenberg et al, 2010 Ann Neurol; Leo et al, 2011 Plos Genet).
FHM type 1 mutations lead to enhanced excitatory synaptic transmission at cortical pyramidal cell synapses without affecting inhibitory synaptic transmission at fast-spiking interneuron synapses; the enhanced glutamate release at cortical synapses may explain the facilitation of CSD (Tottene et al, 2009 Neuron)
FHM type 1 mutations do not affect the functional properties of the CaV2.1 channels expressed in certain types of neurons, including capsaicin-sensitive trigeminal ganglion neurons and multipolar cortical interneurons; as a consequence, CGRP release at trigeminal afferent synapses in the dura mater and GABA release at multipolar interneuron synapses are not altered in FHM type 1 knockin mice (Fioretti et al, 2011 J Physiol; Vecchia et al, 2014 Neurobiol Dis)
D. Pietrobon, B. Prod'hom and P. Hess "Conformational changes associated with ion permeation in L-type calcium channels". Nature (1988) 333, 373-376
D. Pietrobon and P. Hess "Novel mechanism of voltage-dependent gating in L-type calcium channels" Nature (1990) 346, 651-655
L. Forti and D. Pietrobon "Functional diversity of L-type calcium channels in rat cerebellar neurons." Neuron (1993) 10, 437-450
.M.J.M. van den Maagdenberg*, D. Pietrobon*, T. Pizzorusso, S. Kaja, L.A.M. Broos, T. Cesetti, R.A.G. van de Ven, A. Tottene, J. van der Kaa, J.J. Plomp, R.R. Frants, M.D. Ferrari "A cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression." Neuron (2004) 41, 701-710
*Shared first authorship and shared corresponding authorship
A. Tottene A., R. Conti, A. Fabbro, D. Vecchia, M. Shapovalova, M. Santello, AMJM van den Maagdenberg, M. Ferrari M and D. Pietrobon "Enhanced excitatory transmission at cortical synapses as the basis for facilitated spreading depression in CaV2.1 knockin migraine mice." Neuron (2009) 61: 762-773