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The Pitt lab attended the Biophysical Society 60^th Annual Meeting, Los Angeles, Feb 27-March 2, 2016. Both Gavin Robertson and Benedict Reilly-O’Donnell presented their work. Gavin’s poster was entitled ‘Zinc modulates skeletal ryanodine receptor function resulting in altered sarcoplasmic reticulum calcium release’. Gavin is funded by the BHF. Ben presented a poster entitled ‘Diastolic calcium leak and the role of zinc’. Both Gavin and Ben received a travel award from the Physiological Society. Ben also received additional support from the British Society of Cell Biology. The conference was both helpful and informative and we look forward to presenting more data in the future.

Dr Samantha Pitt would like to thank the Royal Society of Edinburgh for awarding her a small equipment grant which will be used to buy a new florescent microscope for the patch rig and for their continued support of her research.

Another fantastic Zinc-UK meeting!

The Pitt and Stewart labs attended the Zinc-UK meeting, London 2015 and would like to thank Dr Imre Lengyel and Dr Elisa Bellomo for putting together such an exciting programme.

Dr Samantha Pitt would like to thank the organisers for giving her the opportunity to talk about the lab’s latest research and gave a talk entitled “Zinc unmasks a new player in cardiac sarcoplasmic reticulum calcium leak”.

Well done to Ben and Gavin who both presented their work at this meeting. Ben gave an oral presentation entitled “The role of zinc in regulating intracellular calcium release” and Gavin presented a poster entitled “A novel role for Zn²⁺ in modulation of sarcoplasmic reticulum calcium release in skeletal muscle”.

The Pitt lab would like to thank the Royal Society of Edinburgh and the BHF for supporting this research.

Another fantastic year.

A special thanks to Alex Street (The Marine Biological Association, Plymouth) and to Prof. David Ogden (Paris Descartes & The Francis Crick Institute, London) for organising another successful year.

2015 was the year of the patch clamp!!! We successfully recorded whole cell currents using both conventional whole cell patch clamp and perforated patch, and also recorded some beautiful single channels using cell attached, outside-out and inside-out patches.

For students thinking of applying or wishing to find out more about the course, please visit Microelectrode Techniques for Cell Physiology 2016

Read our auto-commentary here:

http://www.tandfonline.com/eprint/pPYM3yrf9xVqSjaxncKP/full

Cell Biology of Metals, Gordon Research Conference, 26-31 July 2015

Dr Samantha Pitt would like to thank Profs Amy Palmer and Dennis Thiele for putting together such an exciting programme.

Samantha Pitt presented her work looking at how “Zinc Modulates Cardiac Ryanodine Receptor Function Resulting to Altered Intracellular Ca(II)-Dynamics”

Cardiac excitation-contraction (EC) coupling, a process which governs contractility of the heart, depends on the controlled release of calcium ions (Ca²⁺) from the sarcoplasmic reticulum (SR) through specialised Ca²⁺-release channels called type-2 ryanodine receptors (RyR2). RyR2 plays a pivotal role as the main pathway for the release of Ca²⁺, driving cellular contraction. Consequently, dysfunction in the release of Ca²⁺ through these channels and the modulatory influences which control RyR2 function have been identified as contributory to the pathophysiology of heart failure and fatal cardiac arrhythmias.

Very recently a link between elevated levels of intracellular zinc and heart disease has been highlighted, but very little is understood regarding the role of zinc in the heart. In this latest publication in The Journal of Biological Chemistry the Pitt group show that Zn²⁺ is a high affinity regulator of RyR2 displaying three modes of operation. Picomolar free Zn²⁺ concentrations potentiate RyR2 responses but channel activation is still dependent on the presence of cytosolic Ca²⁺. At concentrations of free Zn²⁺ >1 nM, Zn²⁺ is the main activating ligand and the dependency on Ca²⁺ is removed. Zn²⁺ is therefore a higher affinity activator of RyR2 than Ca²⁺. This work suggest that RyR2-mediated Ca²⁺-homeostasis is intimately related to intracellular Zn²⁺ levels providing a mechanistic explanation linking altered Zn²⁺ homeostasis to cardiac RyR2 function.The data presented represents a shift in our understanding of how RyR2 is activated during EC coupling and indicates that channel dysregulation, through aberrant Zn²⁺ homeostasis, is likely to play a fundamental role in the generation of heart failure and other arrhythmic diseases. Full text is available online.

The Physiological Society, Techniques Workshop – An Introduction to Molecular Biology, UCL, 14-17 april 2015.

Ben and Gavin found the course very informative and enjoyable. The techniques learned have already been used in the lab!

Ben and Gavin would like to thank, the Physiological Society and the course organisers specifically Caroline Pellet-Many who coordinated the whole week.

The Northwood Charitable Trust has just awarded Dr Samantha J. Pitt a small grant (£21,000) titled “Regulation of cardiac function; new mechanisms and novel ion channels”

This research will address the role of zinc signalling in regulating sarcoplasmic reticulum ion-channel function during excitation contraction coupling, and will characterise the potential detrimental role of zinc in cardiomyopathies.

Many thanks for supporting our research.