Samantha Pitt

Samantha-Pitt_photo

Dr. Samantha Pitt

Dr Samantha Pitt

Royal Society of Edinburgh Biomedical Fellow

Principal Investigator

sjp24@st-andrews.ac.uk

Tel: 01334 463156

 

 

 

Research Summary

In healthy individuals, the controlled release of calcium causes the heart to beat strongly. In heart failure and fatal arrhythmias the release of calcium becomes erratic leading to weakened contraction of heart muscle and cell death. Using a combination of low noise electrophysiological recordings in combination with molecular and biochemical methods, my group investigates intracellular calcium dynamics and the molecular function of ion channels that are involved in the control and regulation of calcium-release from intracellular stores. The aim of our research is to try to understand what happens to channel function under pathophysiological conditions.

We currently have two main areas of research:

1. Elucidating the molecular mechanisms of NAADP-regulated signalling via Two Pore Channels

Recent research has discovered that a biological agent called “nicotinic acid dinucleotide phosphate” (NAADP) causes the release of calcium by opening a newfamily of pore forming proteins called two pore channels (TPCs) located on acidic intracellular calcium stores. The mechanism of NAADP-regulated signalling via TPCs is not well understood. In humans there are two isoforms of TPC (TPC1 and TPC2) and we are currently investigating the single-channel behaviour of these putative Ca2+-release channels. Owing to their Ca2+-handling properties aberrant TPC function may impact on diseases where disruption of Ca2+-signals are central, including cytotoxicity and cell death, heart failure, and neurodegenerative processes. Furthermore, genetic studies have linked the gene coding TPC2 to hearing defects and cancer.Understanding the role of TPCs in regulating calcium-release will enable the design of drugs that can manipulate the release of calcium via these channels and help combat diseases associated with abnormal calcium-movements.

2. Understanding new mechanisms of cardiac ryanodine receptor regulation by zinc

We are also interested in how Zn2+ modulates Ca2+-signalling in the heart. Aberrant Zn2+-homeostasis is a hallmark of certain cardiomyopathies associated with altered contractile force and is likely a consequence of altered excitation-contraction coupling. How Zn2+ impacts upon the contractile force and the release of Ca2+ from intracellular stores in cardiac muscle is unknown. Our latest findings suggest that physiological concentrations of Zn2+ modify the function of the cardiac ryanodine receptor Ca2+-release channel (RyR2) and that this change in channel gating may be a major contributor to the generation of cardiac arrhythmias. We are currently investigating at the single-channel level the mechanisms of how Zn2+ regulates RyR function.

Lab Members

External Collaborations

  • Professor Antony Galione – Department of Pharmacology, University of Oxford
  • Dr Richard Rainbow – Department of Cardiovascular Sciences, University of Leicester
  • Professor Rebecca Sitsapesan – Department of Pharmacology, University of Oxford 

Recent Grants

  • SJP is supported by a Royal Society of Edinburgh Biomedical Personal Fellowship
  • Our research is funded by Tenovus Scotland and the British Heart Foundation

Recent Publications

Recent publications


28  (of 28 published available) for sjp24. (source: University of St Andrews PURE)
Please click title of any item for full details.

2018 (6)
Arteriosclerosis, Thrombosis, and Vascular Biology
vol.38 pp.1258-1270
(Review article)
2018 (9)
Metallomics
vol.10 pp.1180-1190
(Review article)
2017 (5/5)
Molecular and Cellular Endocrinology
vol.446 pp.12-20
(Article)
17ß-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats
Sonja Zafirovic, Milan Obradovic, Emina Sudar-Milovanovic, Alexsandra Jovanovic, Julijana Stanimirovic, Alan J. Stewart, Samantha Jane Pitt, Esma R. Isenovic 
Keywords: Estradiol, Obesity, Myocardial metabolism, Cardiovascular diseases, Inducible nitric oxide synthaseQH301 Biology, QH426 GeneticsNDAS
2017 (12)
Molecular and Cellular Biochemistry
vol.436 pp.49-58
(Article)
Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high fat diet
Aleksandra Jovanovic, Milan Obradovic, Emina Sudar-Milovanovic, Alan J. Stewart, Samantha Jane Pitt, Dragan Alvantic, Ema Aleksic, Esma R. Isenovic 
Keywords: High-fat diet, Estradiol, NA+/K+-ATPase, Obesity, RhoA/ROCK signalling, FemaleQH301 Biology, QH426 GeneticsNDAS
2017 (11/8)
Journal of Biological Chemistry
vol.292 pp.13361-13373
(Article)
2017
Current Vascular Pharmacology
vol.15 pp.491-500
(Article)
Influence of a high-fat diet on cardiac iNOS in female rats
Aleksandra Jovanovic, Emina Sudar-Milovanovic, Milan Obradovic, Samantha Jane Pitt, Alan J. Stewart, Sonja Zafirovic, Julijana Stanimirovic, Djordje Radak, Esma R. Isenovic 
Keywords: Cardioprotection, Cardiovascular disease, Oestradiol, Inducible nitric oxide synthase, ObesityQH426 Genetics, RC Internal medicine, RM Therapeutics. PharmacologyNDAS
2017 (6/12)
Scientific Reports
vol.7 
(Article)
Modulation of the Neisseria gonorrhoeae drug efflux conduit MtrE
Giulia Tamburrino, Salome Llabres, Owen Vickery, Samantha Jane Pitt, Ulrich Zachariae 
Keywords: RM Therapeutics. Pharmacology, RC Internal medicine, QH301 BiologyNDAS
2016 (1/4)
Nitric Oxide
vol.54 pp.51-59
(Article)
A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats
Julijana Stanimirovic, Milan M Obradovic, Aleksandra Jovanovic, Emina Sudar-Milovanovic, Sonja Zafirovic, Samantha Jane Pitt, Alan J. Stewart, Esma R Isenovic 
Keywords: High fat diet, Sex differences, Insulin resistance, Liver metabolism, Nitrite/nitrateRM Therapeutics. PharmacologyNDAS
2016 (19/2)
Journal of Biological Chemistry
vol.291 pp.4267
(Letter)
Response to Qian and Colvin
Jason Woodier, Richard D Rainbow, Alan J. Stewart, Samantha Jane Pitt 
Keywords: RM Therapeutics. Pharmacology, QH301 Biology
2015 (1/6)
Biochemical Society Transactions
vol.43 pp.359-363
(Article)
2015 (10/7)
Journal of Biological Chemistry
vol.290 pp.17599-17610
(Article)
2014 (5/5)
Molecular and Cellular Endocrinology
vol.388 pp.58-68
(Article)
In vivo effects of 17β-estradiol on cardiac Na+/K+-ATPase expression and activity in rat heart
Milan Obradovic, Alan J. Stewart, Samantha Jane Pitt, Milica Labudovic-Borovic, Emina Sudar, Voin Petrovic, Sonja Zafirovic, Vera Maravic-Stojkovic, Vesna Vasic, Esma R Isenovic 
Keywords: Estradiol, Sodium potassium adenosine-triphosphatase, Protein kinase B, Extracellular-signal-regulated kinase ½QP Physiology, RC Internal medicine
2014 (18/2)
Biophysical Journal
vol.106 pp.824-833
(Article)
2014 (20/5)
Science Signaling
vol.7 
(Article)
Reconstituted human TPC1 is a proton-permeable ion channel and is activated by NAADP or Ca2+
Samantha Jane Pitt, Andy K M Lam, Katja Rietdorf, Antony Galione, Rebecca Sitsapesan 
Keywords: QP Physiology
2014 (28/1)
Biophysical Journal
vol.106 pp.642A-642A
(Abstract)
TPC1 is a proton permeable channel that can be independently activated by cytosolic calcium or NAADP
Samantha Jane Pitt, Andy Lam, Antony Galione, Rebecca Sitsapesan 
Keywords: QH301 Biology
2013 (8)
Pflügers Archiv: European Journal of Physiology
vol.465 pp.1135-1148
(Article)
TRIC-B channels display labile gating
Elisa Venturi, Antoni Matyjaszkiewicz, Samantha Jane Pitt, Krasimira Tsaneva-Atanasova, Miyuki Nishi, Daiju Yamazaki, Hiroshi Takeshima, Rebecca Sitsapesan 
Keywords: Calcium-release, Ion channel, Excitation-contraction coupling, Sarcoplasmic reticulum
2012 (21/2)
PLoS One
vol.7 
(Article)
FKBP12 activates the cardiac ryanodine receptor Ca2+-release channel and is antagonised by FKBP12.6
Elena Galfre, Samantha Jane Pitt, Elisa Venturi, Mano Sitsapesan, Nathan R Zaccai, Krasimira Tsaneva-Atanasova, Stephen O'Neill, Rebecca Sitsapesan 
Keywords: Calcium-release channel, FKBP, Heart disease, ArrhythmiaR Medicine
2012
Cardiovascular Therapeutics
vol.30 pp.109-16
(Article)
2011
Journal of Membrane Biology
vol.240 pp.21-33
(Article)
2011
Biochemistry
vol.50 pp.2623-32
(Article)
Mitsugumin 23 forms a massive bowl-shaped assembly and cation-conducting channel.
Elisa Venturi, Kazuhiro Mio, Miyuki Nishi, Toshihiko Ogura, Toshio Moriya, Samantha Jane Pitt, Kazutaka Okuda, Sho Kakizawa, Rebecca Sitsapesan, Chikara Sato, Hiroshi Takeshima 
Keywords: MG23, Ion-Channel, Calcium-release
2010
Biophysical Journal
vol.99 pp.417-426
(Article)
Charade of the SR K+-channel
Samantha Jane Pitt, Ki-Ho Park, Miyuki Nishi, Toshiki Urashima, Sae Aoki, Daijyu Yamazaki, Jianjie Ma, Hiroshi Takeshima, Rebecca Sitsapesan 
Keywords: TRIC channels, Sarcoplasmic reticulum, Calcium-homeostasis, Calcium-release
2010 (5/11)
Journal of Biological Chemistry
vol.285 pp.35039-35046
(Article)
TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+
Samantha Jane Pitt, Tim M Funnell, Mano Sitsapesan, Elisa Venturi, Katja Rietdorf, Margarida Ruas, A Ganesan, Rajendra Gosain, Grant C Churchill, Michael X Zhu, John Parrington, Antony Galione, Rebecca Sitsapesan 
Keywords: NAADP, TPC, Calcium-release, Lysosome
2008 (11)
The Journal of Neuroscience
vol.28 pp.11454-11467
(Article)
High intracellular chloride slows the decay of glycinergic currents
Samantha Jane Pitt, Lucia G Sivilotti, Marco B Beato 
Keywords: Glycine, Spinal cord, Motoneuron, Kinetic
2005
Molecular Pharmacology
vol.67 pp.1705-13
(Article)
2003
Blood
vol.102 pp.3646-51
(Article)
Lack of evidence for functional ADP-activated human P2X1 receptors supports a role for ATP during hemostasis and thrombosis.
Catherine Vial, Samantha Jane Pitt, Jon A Roberts, Michael G Rolf, Martyn P Mahaut-Smith, Richard J Evans 
Keywords: P2 receptors, Purine Nucleotides, Platelets, Hemostasis