Amy TseAmy Tse, PhD

Office:     9-70 Medical Science Bldg.
Mail:        University of Alberta, Edmonton Ab T6G 2H7
Phone:     780-492-5796
Fax:         780-492-4325
Email:     
amy.tse@ualberta.ca

 

 

 

 

Current Position

Professor, Dept. of Pharmacology

Research Area

 

Regulation of Calcium signals and exocytosis

 

Current Research Activities

Regulation of pancreatic β cell functions by lipids – rodent study

            A decrease in the ability of β cells to secrete insulin when challenged by an elevation in plasma glucose is a hallmark of type 2 diabetes. This project focuses on understanding the influence of two lipids: arachidonic acid and cholesterol on Ca2+ signaling and exocytosis in pancreatic β cells. 
Time line: 2006 to present

Stage of Project: discovery

Regulation of chemotransduction in carotid bodies – rodent study
            Patients with sleep apnea have a higher risk of type 2 diabetes. The repetitive drop in arterial oxygen level during sleep apnea leads to hyperactivity of the carotid bodies, resulting in an increase in sympathetic drive and development of hypertension and chronic heart failure. This project focuses on understanding the mechanisms that regulate the Ca2+ signals and transmitter release from carotid bodies.

Time line: 2012 to 2015

Stage of Project: discovery

 

Regulation of pituitary hormone secretion – rodent study
            This project focuses on understanding the cellular mechanisms that regulate hormone secretion from two types of pituitary cells: corticotropes and gonadotropes. The secretion of adrenocorticotropic hormone (ACTH) from corticotropes is a key component of the endocrine response to stress. Gonadotropes secrete two hormones: luteinizing hormone and follicle stimulating hormone, which, in turn, regulate sex hormone release.

Time line: 2006 to present
Stage of Project: discovery

 

Other Activities and Affiliations

 

Membership:

  • Canadian Heart & Stroke Foundation scientific review committee III (2008-2010; 2012- 2014)
  • Centre for Neuroscience, University of Alberta
  • General Faculty Council, University of Alberta
  • Nominating committee, Faculty of Medicine, University of Alberta
  • Biophysical Society
  • Society for Neuroscience
  • Endocrine Society

 

Major Achievements

 

Recent Research Highlights:

  • Stimulatory action of arachidonic acid on pancreatic β cells - we found that arachidonic acid triggered a robust Ca2+ rise in β cells via two pathways: extracellular Ca2+ entry via the activation of the highly selective Ca2+-permeable, ARC channels (Cell Calcium 47:77-83; 2010), and intracellular Ca2+ release from an IP3-sensitive acidic store which was probably the secretory granules (Cell Calcium 51: 140-148; 2012). These findings raise the possibility that ARC channels and secretory granules are potential targets for anti-diabetic drugs.
  • Inhibitory actions of cholesterol on pancreatic β cells - we showed that cholesterol elevation reduced glucose-stimulated Ca2+ signaling in mouse β cells via two mechanisms: a reduction in mitochondrial ATP production which was due, in part, to a decrease in glucose uptake; and a reduction in the current density of voltage-gated Ca2+ channels (Endocrinology; 152: 3351-3361; 2011). This finding highlights the importance of reducing cholesterol levels in the prevention of type 2 diabetes.
  • Regulation of Ca2+ signals and exocytosis in corticotropes: We have been studying the cellular mechanisms that regulate adrenocorticotropic hormone (ACTH) release from corticotropes since 1994. Our work reveals how the Ca2+ signal in corticotropes is shaped by different ACTH secretagogues (CRH, AVP and NE) and various Ca2+ transport mechanisms. We have also demonstrated the influence of Ca2+ signal on exocytosis and endocytosis in corticotropes (summarized in Cell Calcium 51: 253-259; 2012). Our work shows that the resting potential of corticotrope is regulated by the two-pore domain, background TREK-1 channels (Endocrinology; 152: 1901-1910; 2011). The activation of TREK-1 channels by arachidonic acid raises the possibility that arachidonic acid acts as a negative feedback to prevent excessive ACTH release during chronic stress.

 

Biography

Dr. Tse obtained a BSc. in Pharmacy (University of Toronto) and then a Ph.D. in Physiology (University of Calgary). Following her postdoctoral fellowship with Professor Bertil Hille at the University of Washington, she joined the Department of Pharmacology in 1994 as an assistant professor and AHFMR Scholar, CIHR Scholar and HSFC Scholar.  She has been a professor since 2007. Her major research interest is the regulation of Ca2+ signals and exocytosis in endocrine and neuroendocrine cells. Her laboratory employs a repertoire of biophysical techniques, including patch clamp recordings for measurement of currents and membrane potential, capacitance measurement for monitoring exocytosis from single cells, carbon fiber amperometry for measurements of quantal catecholamine release, flash photolysis of caged compounds, and measurements of cytosolic [Ca2+] and mitochondrial [Ca2+] with fluorescent indicators.

 

Research Goals

 

Our goal is to understand the factors that affect hormone secretion. Such knowledge will aid in the development of drugs to increase or reduce the secretion of specific hormones. For example, in the context of diabetes, we have found that excessive cholesterol reduces the ability of β cells to secrete insulin but arachidonic acid can stimulate insulin secretion. This knowledge will be valuable in the development of specific drugs for the treatment of type 2 diabetes.

 

Selected Publications

 

  1. Yeung-Yam-Wah V, Lee AK, Tse FW & Tse A (2010).  Arachidonic acid stimulates extracellular Ca2+ entry in rat pancreatic β cells via activation of the noncapacitative arachidonate-regulated Ca2+ (ARC) channels.  Cell Calcium 47:77-83.  PMID:20018371
  2.  Wang N, Kwan C, Gong X, Posse de Chaves E, Tse A & Tse FW (2010). Influence of cholesterol on catecholamine release from the fusion pore of large dense core chromaffin granules. Journal of Neuroscience 30: 3904-3911.  PMID:20237261
  3.  Lee AK, Smart JL, Rubinstein M, Low MJ & Tse A.  (2011) Reciprocal regulation of TREK-1 channels by arachidonic acid and CRH in mouse corticotropes. Endocrinology 152: 1901-1910.  PMID:21343252
  4. Lee AK, Yeung-Yam-Wah V, Tse FW & Tse A. (2011) Cholesterol elevation impaired glucose-stimulated Ca2+ signaling in mouse pancreatic β cells. Endocrinology 152: 3351-3361. PMID: 21712366
  5. Yeung-Yam-Wah V, Lee AK & Tse A. (2012) Arachidonic acid mobilizes Ca2+ from the endoplasmic reticulum and an acidic store in rat pancreatic beta cells. Cell Calcium 51: 140-148. PMID: 22197025
  6. Yan L, Lee AK, Tse F & Tse A. (2012) Ca2+ homeostasis and exocytosis in carotid glomus cells: role of mitochondria. Cell Calcium 51: 155-163. PMID: 22209034
  7. Tse A, Lee AK & Tse FW (2012) Ca2+ signaling and exocytosis in pituitary corticotropes. Cell Calcium 51: 253-259. PMID: 22225940
  8. Tse A, Yan L, Lee AK & Tse FW (2012) Autocrine and paracrine actions of ATP in rat carotid body. Canadian Journal of Physiology and Pharmacology 90: 705-711. PMID: 22509744
  9. Tse A, Lee AK, Yan L & Tse FW (in press) Influence of Cholesterol on Cellular Signaling and Fusion Pore Kinetics. Journal of Molecular Neuroscience  PMID:22467040

 

 

Trainees

 

  • Andy K. Lee – research associate
  • Lei Yan – Ph.D. student
  • Su-Su Ling - MSc student