Brain temperature regulation in mammals: mechanisms and consequences. Mammals detect increases in body temperature predominantly in the brain. Counterintuitively many mammals selectively cool the brain during heat stress, which appears to defeat the mechanism for inducing cooling responses. We intend to investigate this apparent anomaly which we believe is concerned with optimizing water use in hot conditions. We will further investigate the source of water for evaporative cooling by panting and ....Brain temperature regulation in mammals: mechanisms and consequences. Mammals detect increases in body temperature predominantly in the brain. Counterintuitively many mammals selectively cool the brain during heat stress, which appears to defeat the mechanism for inducing cooling responses. We intend to investigate this apparent anomaly which we believe is concerned with optimizing water use in hot conditions. We will further investigate the source of water for evaporative cooling by panting and discover if there has been convergent evolution in thermoregulatory strategies in the eutherian and marsupial lineages. The data we collect will be used to support a new model for thermoregulation in mammals.
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Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is ....Resurgent Sodium Currents in Peripheral Nerve Axons and Sensory Neurones. This project seeks evidence that unusual gating of sodium channels contributes to the hyperexcitability that results in spontaneous impulse activity in sensory axons. It asks whether axons normally behave as if they have this gating mode, whether it can be induced, whether any such behaviour is more prominent with sensory axons than motor, and whether the current can be measured directly in sensory neurones. The project is the first to involve correlation of patch-clamp recordings with the behaviour of intact axons. Its outcomes will affect thought about sodium channel behaviour and may alter approaches to disorders of axonal excitability.Read moreRead less
Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory ....Anandamide activated chloride channels in sensory neurons. We are seeking to understand how the nerve cells that sense our environment are regulated by signalling molecules produced by our body. Understanding how these cells function in normal conditions is essential as basis for understanding how they may function abnormally in physically stressful situations or in chronic pain conditions. The work may eventually lead to better treatments for a wide range of disorders that involve the sensory nervous system. Read moreRead less
Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric ....Regulation of large artery stiffness by endothelium-derived mediators and effects on the arterial pressure waveform. Stiffening of arteries is an important cardiovascular risk factor and increases with age, high blood pressure, high cholesterol and diabetes. Cells that line the blood vessels (endothelial cells), become damaged and this reduces the available amount of a dilator substance, nitric oxide, and increases the activity of a constrictor substance, endothelin-1. We have shown that nitric oxide regulates large artery stiffness and we believe that other endothelial mediators are also important regulators. Therefore, we aim to explore this in a series of studies. Regulation of stiffness of large arteries will improve treatment of age-related cardiovascular disease (eg isolated systolic hypertension)Read moreRead less
Physiological significance of transient receptor potential (TRPC3) ion channels in the cochlea. The project seeks to discover the function of transient receptor potential (TRPC3) ion channels in the cochlea. Recent studies have suggested that these proteins, which are expressed by the sensory and neural cells, are key elements regulating sound transduction and neurotransmission. The new knowledge about the physiological processes underlying hearing that this work will provide, will significantl ....Physiological significance of transient receptor potential (TRPC3) ion channels in the cochlea. The project seeks to discover the function of transient receptor potential (TRPC3) ion channels in the cochlea. Recent studies have suggested that these proteins, which are expressed by the sensory and neural cells, are key elements regulating sound transduction and neurotransmission. The new knowledge about the physiological processes underlying hearing that this work will provide, will significantly benefit national and international translational research that seeks to develop systems for controlling the sensitivity of our senses, developing biosensors, interacting with neural networks and developing neural prostheses. International collaborators in this project have enabled development of new models, technology and research training opportunities.Read moreRead less
Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin abso ....Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin absorbs light: e.g. intermediates such as metarhodopsin and opsin. The molecular knowledge obtained will help us to understand why it is that the visual system recovers so slowly after the eye has experienced very intense light.Read moreRead less
Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechan ....Investigating the mechanisms of flavonoid actions on glycine receptors. The research to be conducted in this project will use state-of-the-art electrophysiological and molecular biological approaches to carefully characterise the actions of certain flavonoid compounds on the glycine-receptor channel. These compounds have recently been reported to act as modulators of ligand-gated ion channels, proteins integral to brain function and disease. However, no-one has studied in any detail the mechanisms by which these compounds act. By discovering their site and mechanisms of action we will further our understanding of these important proteins and their modulation, maintain Australia's significant expertise in this field and provide leads for future development of drugs with potential therapeutic value.Read moreRead less
How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Buil ....How triadin and junctin communicate with ryanodine receptors deep within a calcium store to determine skeletal muscle contraction. The project results will provide a platform for muscle relaxants and other drugs that will specifically target either the heart or skeletal muscle and will have applications in the livestock, veterinary and pharmaceutical Industries. The project falls within the National Research Priorities of Promoting and Maintaining Good Health and Frontier Technologies for Building and Transforming Australian Industries, as well as the national priority goal of Ageing well, Ageing Productively. The project will be of national benefit in training undergraduate students, PhD students and a postdoctoral fellow in state-of-the-art techniques in an internationally competitive research field.Read moreRead less
Calcium Signalling and Sequestration at Vertebrate Motor-Nerve Terminals. A fundamental process at Synapses is the release of transmitter from nerve terminals due to the initiation of calcium signalling in the temrinals by impulses. This calcium signalling must be terminated by sequestering processes. The aim of this project is to identify these processes in a vertebrate motor-nerve terminal and to determine the means by which calcium signals the changes in efficacy of transmitter release during ....Calcium Signalling and Sequestration at Vertebrate Motor-Nerve Terminals. A fundamental process at Synapses is the release of transmitter from nerve terminals due to the initiation of calcium signalling in the temrinals by impulses. This calcium signalling must be terminated by sequestering processes. The aim of this project is to identify these processes in a vertebrate motor-nerve terminal and to determine the means by which calcium signals the changes in efficacy of transmitter release during trains of impulses. This work will give a complete description of calcium signalling in a vertebrate nerve terminal and provide the basis for ameliorating failures in transmission from nerve to muscle.Read moreRead less
Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable ....Involvement of cell coupling in vascular function: Development of a computational model. Gap junctions are intercellular channels which enable the production of coordinated responses in multicellular tissues and organs. Blood vessels are comprised of endothelial cells surrounded by smooth muscle cells and gap junctions exist within and between these layers. The present proposal will determine the fundamental role of gap junctions in regulating blood flow and blood pressure. Our data will enable us to develop a computational model of the vascular wall and so predict how changes in electrical properties, as occur during pressure changes, can influence blood flow. Since ageing is accompanied by an increase in blood pressure, our results will contribute to a better understanding of blood flow regulation in our ageing population.Read moreRead less