Intramuscular Interstitial Cells Of Cajal; Ion Channels And Their Modulation By Calcium Ions And Neurotransmitters.
Funder
National Health and Medical Research Council
Funding Amount
$523,261.00
Summary
Disorders of gut motility manifest themselves in several ways, as either patterns of hyperactivity or patterns of reduced activity. Under normal conditions gut motility reflects a balance between myogenic, neuronal and hormonal factors but as yet how this balance is normally achieved is not understood. This project will examine the properties of a class of cells, whose importance in both myogenic and neural control mechanisms has only been recognized over the last 10 years. The muscular wall of ....Disorders of gut motility manifest themselves in several ways, as either patterns of hyperactivity or patterns of reduced activity. Under normal conditions gut motility reflects a balance between myogenic, neuronal and hormonal factors but as yet how this balance is normally achieved is not understood. This project will examine the properties of a class of cells, whose importance in both myogenic and neural control mechanisms has only been recognized over the last 10 years. The muscular wall of the gut is made up of two distinct types of cells. One group, smooth muscle cells, contains contractile elements and the coordinated behavior of these cells leads to the contractions of the gut wall, so ensuring the controlled passage of gut contents along the gastrointestinal tract. The other group of cells, Interstitial cells of Cajal, lack contractile elements. One set of these cells have recently been found to be the pacemaker cells of the gut responsible for the initiation of myogenic activity. They generate pacemaker waves which ensure that the gut contracts rhythmically. Another set of these cells are densely innervated, they receive messages from the nervous system and translate these messages into signals which alter the activity of the gut. Thus these cells play a key role in the neural control of the gut. In many disease states, the numbers of interstitial cells of Cajal have been found to be reduced. However as yet we know very little about these cells. This project will, for the first time, examine the properties of the interstitial cells involved in neural control and will determine how they carry out these essential functions.Read moreRead less
Control Of Gastrointestinal Motility By Interstitial Cells And Neuronal Projections
Funder
National Health and Medical Research Council
Funding Amount
$845,540.00
Summary
The gastrointestinal tract moves contents along its length in an ordered manner, so allowing digestion and absorption of gut contents. These movements are controlled by the properties of the cells in the muscle layers which in part make up the wall of the gastrointestinal tract, by activity in the nerves that innervate the gut and by hormonal factors. Recently we have shown that a key part of the control system lies in a set of special cells, interstitial cells, that lie amongst the muscle cells ....The gastrointestinal tract moves contents along its length in an ordered manner, so allowing digestion and absorption of gut contents. These movements are controlled by the properties of the cells in the muscle layers which in part make up the wall of the gastrointestinal tract, by activity in the nerves that innervate the gut and by hormonal factors. Recently we have shown that a key part of the control system lies in a set of special cells, interstitial cells, that lie amongst the muscle cells. This project will determine how these cells exert their control. These cells generate large long lasting waves of voltage which flow to nearby muscle cells so causing them to contract. The first aim is to determine how the special cells generate the command signals and the second aim is to determine how the signals spread to the muscle cells. The subsequent section of the project will determine how the behavior of the cells in the gastrointestinal tract are controlled by nervous influences. Disorders of the intestine are frequent and these appear to involve disrupted muscle contraction either because the intrinsic control system is malfunctioning or because the nervous system is unable to exert its normal influence. This project will determine how the normal control system works, invariably when this has been done with other systems, disease states are easier to rectify.Read moreRead less
How Does The Mitochondria Regulate Cardiac L-type Ca2+ Channel Function?
Funder
National Health and Medical Research Council
Funding Amount
$328,267.00
Summary
Oxygen is vital to cellular metabolism and function. Oxygen delivery to cells is critical and a lack of oxygen such as occurs during a heart attack can be lethal. The L-type Ca2+ channel is a protein in the membrane of heart muscle cells responsible for regulating the entry of calcium into heart muscle cells. It plays a role in maintaining the heart beat and contraction. We have found that a lack of oxygen (hypoxia) alters the function of the L-type Ca2+ channel and its response to adrenergic st ....Oxygen is vital to cellular metabolism and function. Oxygen delivery to cells is critical and a lack of oxygen such as occurs during a heart attack can be lethal. The L-type Ca2+ channel is a protein in the membrane of heart muscle cells responsible for regulating the entry of calcium into heart muscle cells. It plays a role in maintaining the heart beat and contraction. We have found that a lack of oxygen (hypoxia) alters the function of the L-type Ca2+ channel and its response to adrenergic stimulation (adrenaline).This may be one of the ways that rhythm disturbances or sudden cardiac death occurs with a heart attack. The activity of the L-type Ca2+ channel is sensitive to changes in reactive oxygen species caused by changes in oxygen concentration. The reactive oxygen species are generated from a part of the cell responsible for maintaining the cell's energy requirements (the mitochondria). Oxidative stress is a feature of various cardiovascular pathologies and we are now interested in determining the effect of oxidative stress on function of the L-type Ca2+ channel and the role of the mitochondria in generating reactive oxygen species. Oxidative stress can damage mitochondria leading to an increase in production of reactive oxygen species. We will determine how oxidative stress damages the mitochondria and how this then alters the channel function, directly or indirectly. The information gained will provide insight into how reactive oxygen species influence L-type Ca2+ channel function and the mechanisms that contribute to pathology involving reactive oxygen species such as heart failure and arrhythmia.Read moreRead less