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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.

Was great meeting all of the S4 pupils from St Andrews High, Kirkcaldy, at the routes into employment STEM “speed dating” event yesterday. I hope they enjoyed it as much as I did. I wish them all the best in their future careers. – Dr Samantha J. Pitt

Dr Samantha Pitt and Dr Alan Stewart would like to thank the British Heart Foundation for supporting their research titled “Understanding new mechanisms of cardiac ryanodine receptor regulation by zinc”. These funds will support Gavin Robertson during his PhD research.

Gavin starts his PhD today!

The first Zinc-NET workshop was held at the Institute of Ophthalmology, at University College London, 4th and the 5th of November.

There was an impressive line-up of speakers who discussed how to measure zinc and a “hands-on ” session for the participants. Dr Samantha Pitt would like to thank the organisers, tutors and speakers for a highly informative and thought provoking session.

For more info visit zinc-net: http://zinc-net.com

The Stewart and Pitt labs would like to congratulate Gavin on obtaining his MRes.

Well done Gavin you did a great job.

The calcium signalling meeting was a huge success. A very enjoyable and informative meeting.

Thanks to Prof. Sandip Patel and Dr Grant Churchill for putting together such an exciting programme.

Dr Samantha Pitt would like to thank the organisers for giving her the opportunity not only to present her work but also to chair a session for the first time!