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
Neural Control Of Colorectal Function And Identification Of Sites Of Drug Action
Funder
National Health and Medical Research Council
Funding Amount
$375,489.00
Summary
Constipation is a considerable problem, especially in the elderly; it occurs in 20-25% of people over 65 and in about 50% of people in nursing homes. It is also a significant concern for children, with up to 30% being affected. There are no adequate treatments and the majority of people are dissatisfied with their management. We have discovered a class of compounds that stimulate defecation. In this project we will test the effectiveness of these compounds to relieve constipation.
The Splanchnic Anti-inflammatory Pathway: The Real Inflammatory Reflex
Funder
National Health and Medical Research Council
Funding Amount
$613,466.00
Summary
The brain strongly influences immune function through a neural reflex: the inflammatory reflex. This reflex was recently revised and a new model for its efferent arm, in stark contrast with the existing version, was proposed: the motor pathway of this reflex is purely sympathetic and travels through the splanchnic nerves. The aim of this project is to define the peripheral and central neural pathway of this reflex. Future improvements in health and medical knowledge will follow
How Intestinal Motility Activates Sensory Pathways
Funder
National Health and Medical Research Council
Funding Amount
$555,875.00
Summary
Pain and discomfort from the gut are common and unpleasant. We understand how gut sensory nerve cells work, at the cellular, molecular and genetic level. However, movement of the gut wall and contents are the major cause of activation of sensory neurons. We know little about which particular patterns of movement cause pain. This is crucial information for accurately diagnosing human gut disorders, for monitoring effectiveness of treatments and for identifying potential new drug targets.
Imaging The Activation Of Sensory Nerve Endings That Detect Pain In The Colorectum
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Within the gastrointestinal tract are sensory nerve endings that detect painful stimuli. In this project a new technique has been developed that allows us to monitor and record the activation of the particular sensory nerve endings that detect painful stimuli. This project will determine how these sensory nerve endings detect pain and how drugs might be used to relieve these unpleasant sensations arising from the gut wall.
Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypotheses that this pacemaker mechanism is also fundamental to mammalian heart pacemaking and conduction. Positive support for our hypotheses, as indicated by our findings on amphibian hearts and from pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less