Calcium Signalling Laboratory

Confocal images of the plasma membrane of liver cells transfected with a GFP-tagged plasma membrane reporter

Signals conveyed from one part of the body to another, require the release of chemical messengers (hormones and neurotransmitters) from one set of cells and their action on target cells. The processes by which hormones and neurotransmitters act on target cells require increases in the concentration of calcium ions in the target cell. This is often achieved by calcium entering the cell through channels in the plasma membrane. The aims of this research is to study the physiological functions of these calcium channels, their structures and mechanisms of opening, and how these channels are altered in diseased states.

Investigators

Greg Barritt, BSc(Hons), PhD

Visiting Research Scholars

Judith ten Berge, University Medical Centre, Netherlands
Ruth Versteeg, University of Amsterdam, Netherlands
Max Madu, University Medical Centre, Groningen, Holland
Willem Rademacher, University Medical Centre, Groningen, Holland
Andy Miller, Biology, Hong Kong University of Science and Technology

Support Staff

Claire Wilson, BSc(Hons)

Students

Brian Tam, PhD Student
Eunus Ali, PhD Student
Farhana Afroz, PhD Student
Rupinder Singh, MBiotech Student

Contacts

Prof Greg Barritt

Ph: (08) 8204 4260 or (08) 8204 4419
Int Ph: +61 8 8204 4260 or +61 8 8204 4419
Fax: (08) 8374 0139
Int Fax: +61 8 8374 0139
Email: greg.barritt@flinders.edu.au
University Profile Page

Research Projects

Receptor-activated calcium channels
There is now considerable evidence that most cells possess receptor-activated Ca(2+) channels as well as voltage-operated Ca(2+) channels. However, the structures and mechanisms of activation of receptor-activated Ca(2+) channels are not well understood. Recently it has been shown that store-operated Ca(2+) channels (STIM1 and Orai1) and members of the TRP (transient receptor potential) channel family are important receptor-activated Ca(2+) channels in animal cells. Mutations in TRP channels may be responsible for some forms of photoreceptor cell and neuronal cell degeneration. The aims of this research are to (i) study the roles of STIM and Orai proteins in store-operated Ca(2+) channels and (ii) to identify TRP channels in non-excitable and excitable cells. Messenger RNA encoding subtypes of TRP channels have been identified using RT-PCR techniques, and some of the TRP proteins have been detected by (a) using specific antibodies directed against the proteins and (b) functionally. Experiments are presently under-way to further elucidate the physiological functions of these TRP channels.

Collaborative Research

Dr Grigori Rychkov, Dr Michael Roberts and Dr Tom Litjens, University of Adelaide: Store-operated calcium channels.

Dr Vincent Nieuwenhuijs and Prof Robert Porte, University Medical Centre, Groningen, Holland: Ischemic reperfusion injury.

Dr Andy Miller and Dr Sarah Ho, The Hong Kong University of Science & Technology: Calcium signalling in zebra fish liver.

Selected Recent Publications

Steenks M, Baal V, Nieuwenhuijs V, De Bruijn M, Schiesser M, Teo EH, Callahan T, Padbury RT & Barritt GJ (2010) Intermittent ischaemia maintains function after ischaemia reperfusion in steatotic livers. Journal of Hepato-Biliary-Pancreatic Surgery. 12(4), 250-261

To M-S, Aromataris EC, Castro J, Roberts ML, Barritt GJ and Rychkov GY (2010) Mitochondrial uncoupler FCCP activates proton conductance but does not block store-operated Ca(2+) current in liver cells. Arch. Biochem. Biophys, 495:152-158

Castro J, Aromataris EC, Rychkov GY and Barritt GJ (2009) A small component of the endoplasmic reticulum is required for store-operated Ca2+ channel activation in liver cells: evidence from studies using TRPV1 and taurodeoxycholic acid. Biochem. J. 418, 553-566

Peters J, Nieuwenhuijs VB, Morphett A, Porte RJ, Padbury RTA and Barritt GJ (2009) Increasing cycles of intermittent ischemia can effectively maintain liver function during the acute phase of ischemia reperfusion injury by promotion of bile flow and reduction in bile salt toxicity. Dig. Surg. 26, 455-464

de Vries AH, Ponds FAM, Padbury RTA ,Porte RJ, Nieuwenhuijs VB and Barritt GJ (2009) Influence of estrogen on the early recovery of hepatobiliary secretory function after ischemia reperfusion injury in rats. J. Hepatol. 50(Supp 1), S66

Wigg AJ, Barritt GJ, Young GP and Phillips JW (2009) Inhibition of oxidative stress and apoptosis enables extended maintenance of integrity and function of isolated hepatocytes in suspension. J. Gastroenterol. Hepatol. 24, 1082-1088

Schiesser M, Wittert A, Nieuwenhuijs VB, Morphett A, Padbury RTA and Barritt GJ (2009) Intermittent ischemia but not ischemic preconditioning is effective in restoring bile flow after ischemia reperfusion injury in the livers of aged rats. J. Surg. Res. 152, 61-68

Scrimgeour N, Litjens T, Ma L, Barritt GJ and Rychkov TY (2009) Properties of Orai1 mediated store-operated current depend on the expression levels of STIM1 and Orai1 proteins. J. Physiol. 587, 2903-2918

Zeile S, Wilson C, Chataway T, Nieuwenhuijs VB, Padbury RTA and Barritt GJ (2009) Proteomic analysis reveals modulation of peroxiredoxin 1 following ischemia reperfusion injury of liver. J. Hepatol. 50(Supp 1), S64

Barritt GJ, Litjens TL, Castro J, Aromataris E and Rychkov GY (2009) Store- operated Ca2+ channels and microdomains of Ca2+ in liver cells. Clin. Exp. Pharmacol. Physiol. 36, 77-83

Barritt GJ, Chen J and Rychkov GY (2008) Ca 2+-permeable channels in the hepatocyte plasma membrane and their roles in hepatocyte physiology. Biochem Biophys Acta - Mol Cell Res, 1783, 651-672

Aromataris EC, Castro J, Rychkov GY and Barritt GJ (2008) Store-operated Ca 2+ channels and stromal interaction molecular 1 (STIM1) are targets for the actions of bile acids on liver cells. Biochem Biophys Acta - Mol Cell Res, 1783, 874-885

Khung YL, Barritt G and Voelcker NH (2008) Using continuous porous silicon gradients to study the influence of surface topography on the behaviour of neuroblastoma cells. Exper Cell Res, 314, 789-800

Beck B, Bavencoffe A, Bidaux G, Lemonnier L, Thebault S, Shuba Y, Barritt G, Skryma R and Prevarskaya N (2007) Prospects for prostate cancer imaging and therapy using high-affinity TRPM8 activators. Cell Calcium 41:285-94

Nieuwenhuijs VB, de Bruijn MT, Schiesser M, Morphett A, Padbury RT, Barritt GJ (2007) Ischemic preconditioning and intermittent ischemia preserve bile flow in a rat model of ischemia reperfusion injury. Dig Dis Sci. 52(5):1159-67

Litjens T, Nguyen T, Castro J, Aromataris EC, Jones L, Barritt GJ, Rychkov GY (2007) Phospholipase C-gamma1 is required for the activation of store-operated Ca2+ channels in liver cells. Biochem J. 405(2):269-76

Rychkov G, Barritt GJ (2007) TRPC1 Ca(2+)-permeable channels in animal cells. Handb Exp Pharmacol. (179):23-52. Review

Prevarskaya N, Zhang L, Barritt G (2007) TRP channels in cancer. Biochem Biophys Acta 1772:937-46