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
Vasomotor Ganglionic Transmission: The Preganglionic Peptide And The Second Gear
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Blood pressure depends on nerve signals that travel from the central nervous system to blood vessels. In the middle of this pathway is a relay station - the sympathetic ganglion cell. Transmission through this relay station has recently been shown to have not only a fixed but also a variable component - the 'second gear'. The project tests if and how three likely candidate peptide molecules, one in the nerves, two in the bloodstream, control this 'second gear' and hence regulate blood pressure.
Regeneration Of Pelvic Autonomic Axons After Injury
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
This project is focused on the problem of erectile dysfunction, especially the common situation where this is caused by injury to the penile nerves. These nerves are part of the parasympathetic nervous system . Nerve injury-induced erectile dysfunction is a common problem for prostatectomy patients, with recovery of normal erections occurring slowly, partially or not at all. There is currently no therapy to improve regeneration of these nerves, and this is partly because very little is known abo ....This project is focused on the problem of erectile dysfunction, especially the common situation where this is caused by injury to the penile nerves. These nerves are part of the parasympathetic nervous system . Nerve injury-induced erectile dysfunction is a common problem for prostatectomy patients, with recovery of normal erections occurring slowly, partially or not at all. There is currently no therapy to improve regeneration of these nerves, and this is partly because very little is known about effects of injury on any parasympathetic neurons, and especially for those that are essential for erection. The first aim of this study is to define the key structural and functional changes occurring in penile parasympathetic neurons during regeneration after injury. This fundamental neurobiological knowledge is essential to develop and optimise an future growth treatments. The second aim of the study is to define the effects of a protein, neurturin, on axonal regeneration of penile pro-erectile neurons. Our evidence so far strongly suggests that it is necessary for the early stages of injury responses. Our studies will be performed in mice, where we also have colonies of knockout animals to study the effect of removing neurturin from the regeneration process. Our experiments will include neuroanatomical studies of injured and growing nerves, pharmacology studies on penile smooth muscle (corpus cavernosum) innervation and responsiveness, and tissue culture studies. We will investigate not only the changes that occur following injury to penile nerves, but also the way in which undamaged nerves may assist in returning erectile function.Read moreRead less
Investigations Of Mechanisms Underlying Autonomic Cardiovascular Regulation In Medial Temporal Lobe Epilepsy.
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
People with epilepsy often show disturbed cardiovascular function which may increase mortality risk. This may reflect seizure related disturbances in the autonomic circuitry regulation of the cardiovascular system. We apply advanced brain imaging analysis of altered neural structure, circuit connectivity and function within medial temporal lobe and mid brain, combined with clinical assessment of autonomic function to provide important new insights into cardiac disturbances in epilepsy.