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
Rhythmicity And Synchronicity In Uterine Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$291,823.00
Summary
Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that ....Natural birth occurs through rhythmic contractions of the smooth muscle of the uterus. There is surprisingly little understanding of the mechanism of the pacemaker clock that both initiates and times each contraction in a coordinated manner to expel the fetus. This project is to challenge this knowledge gap using our findings on cellular rhythms that herald Ca2+ stores as a major pacemaker mechanism. First, we will use electrophysiology and calcium imaging techniques to test the hypothesis that rhythmicity and synchronicity of uterine contractions are underpinned by store pacemaking. Second, we will probe the role of current spread between cells via gap junctions as a mechanism of recruitment and will examine whether accessory cells termed interstitial cells subserve a role in pacemaking. These cells are present within the uterine wall but their function is unknown. We will probe their ion channel properties in relation to pacemaking using patch clamp techniques. Third, we will examine the role of labour hormones, such as oxytocin, in augmenting uterine contractions via interaction with the Ca2+ store mechanism and cell recruitment. These studies will provide new and fundamental insights into uterine pacemaking, an outcome that should be of great significance to understanding and better controlling birth-associated complications such as preterm delivery and failure to progress.Read moreRead less