Dr Marie-Louise Ward

PhD Auck.

Research | Current

Cytoplasmic calcium (Ca2+) concentration underlies many important physiological activities, including muscle contraction. My research area is in the regulation of intracellular Ca2+ homeostasis in cardiac muscle, and the influence of other intracellular ions (such as Na+ and H+) on Ca2+ regulation. There is much evidence to indicate that abnormal Ca2+ handling underlies many cardiac pathologies. We use spectrofluorometric techniques to record rapid changes in intracellular ions associated with the regulation of excitation-contraction coupling in isolated cardiomyocytes or trabeculae. Trabeculae are small (typically 100-200 µm in diameter, and ~2 mm long), multicellular muscles with the myocytes aligned along the longitudinal axis. This property makes them ideal for mechanical measurement of contractile function. They can be attached to a force transducer, mounted in a muscle chamber on the stage of an inverted microscope, and stimulated electrically to contract. Their small cross-sectional area minimises diffusion distances and allows them to be kept alive for many hours by superfusing with oxygenated physiological solution. It is easy also to monitor the muscle's response to different pharmacological agents by addition of these to the superfusate. Most importantly, trabeculae can be loaded with fluorescent indicators, so that simultaneous measurement of isometric force and intracellular ions can be made.

We routinely combine our measurements of intracellular Ca2+ and force with high resolution measurements of mitochondrial function (Oxygraph-2K) in tissue from the same hearts. Cardiomyocytes have abundant mitochondria which provide the energy (in the form of ATP) that fuels the heart's contraction, as well as buffering cytosolic Ca2+and regulating the redox state of the cell. Micrographs of healthy hearts show the mitochondria arranged in a ‘crystal-like structure’ adjacent to the contractile proteins, but in failing hearts this structure appears disorganized. While mitochondrial function in terms of decreased respiration has been demonstrated extensively in the literature, the mechanisms by which this contributes to the depressed contractility of failing hearts are not fully understood. To this end we will investigate how ultra-structural and functional changes of mitochondria within cardiomyocytes contribute to the production and transfer of energy (in the form of ATP) to sites of high consumption including the sarcoplasmic reticulum and myofibrils and how this influences Ca2+handling and force production.

Current projects

  • Ca2+ handling in pulmonary hypertension and RV hypertrophy
  • Mitochondrial energy supply in failing hearts
  • Regulation of cardiac contractility
  • Stretch and the Heart
  • Diabetic heart disease
  • Examination of the beta-adrenergic response in diabetic hearts 

Research interests

  • Cardiac force-length relationship
  • Slow force respone to stretch
  • Cardiac muscle function
  • Hypertensive heart failure
  • Diabetic cardiomyopathy
  • Atrial fibrillation

Teaching | Current

MEDSCI 205 Organ Systems Physiology, Respiratory module

PHARMACY 311 Respiratory and Cardiovascular modules

MEDSCI 309 Biophysics of Nerve & Muscle, Course Director

MBCHB 221 Musculoskeletal, Cardiovascular and Respiratory courses.

MEDSCI 733 Live Cell Imaging

Postgraduate supervision

Year

Student Name

Programme

Role

2021

Krstic, Anna

PhD

Primary supervisor

2021

Jones, Timothy

PhD

Primary supervisor

2021

Musgrave, Julia

PhD

Co-supervisor

 

 

Responsibilities

  • PI of Muscle Cell Function Research Group
  • Senior Lecturer in Physiology

Areas of expertise

 Langendorff perfused hearts, isolated trabeculae and cardiomyocytes used to study:

  • Excitation-contraction coupling.
  • Structure and function.
  • Mitochondrial respirometry.

Committees/Professional groups/Services

Secretary of New Zealand Society for Medical Sciences Inc. from 2019.

Organising committee Co-Chair for Medical Sciences Congress, Queenstown, New Zealand, 2017 - 2019. 

Member International Society for Heart Research since 1999,  & Council Representative from 2007 – 2016 (Australasian Branch). 

1992 - present  Member New Zealand Physiological Society. Treasurer  from 2013-2018.

Selected publications and creative works (Research Outputs)

As of 29 October 2020 there will be no automatic updating of 'selected publications and creative works' from Research Outputs. Please continue to keep your Research Outputs profile up to date.

Identifiers

Contact details

Primary office location

M&HS BUILDING 503 - Bldg 503
Level 4, Room 401D
85 PARK RD
GRAFTON
AUCKLAND 1023
New Zealand

Web links