Biomedical subjects

Susan Wray

Publications and source records attributed to Susan Wray.

40 records · Page 3Linked to original sources

PubMed2002

Prenatal LHRH neurons in nasal explant cultures express estrogen receptor beta transcript.

Sex steroids influence LHRH neuronal activity, exerting a negative or positive feedback action, depending on the reproductive state of the animal. Recent evidence indicates that LHRH neurons possess the estrogen receptor beta (ERbeta) subtype postnatally, suggesting that estrogen may act, in part, directly on LHRH neurons. In this study, we identified ERbeta transcript in prenatal LHRH neurons as a function of age. Single-cell cDNA pools were made from LHRH neurons maintained for 7, 14, and 28 d in vitro (div). Screening of the cDNA pools by PCR with ERbeta-specific primers revealed ERbeta-positive LHRH neurons at all three ages. However, the number of LHRH cells coexpressing ERbeta transcript decreased dramatically between 14 (6/10) and 28 div (1/10). None of the LHRH cells were positive for ERalpha transcript. These results indicate that developing LHRH neurons express the transcript for ERbeta and suggest that continued expression of ERbeta is either a characteristic of LHRH neurons that may require cues from the central nervous system and/or periphery or predetermined to be maintained in a subpopulation of LHRH neurons.

Animals↗

PubMed2002

Sarcoplasmic reticulum function and contractile consequences in ureteric smooth muscles.

This paper discusses the role of Ca2+-induced Ca2+ release (CICR) and inositol-1,4,5-trisphosphate (InsP3)-induced Ca2+ release (IICR) from the sarcoplasmic reticulum (SR) in the control of contractile activity in the ureter. The Ca2+ store in guinea-pig ureter has been found to be exclusively a CICR type with ryanodine receptors (RyRs) present. In the rat ureter the SR store is exclusively an IICR type with InsP3 receptors (InsP3Rs) present. Guinea-pig ureteric cells in vitro and in situ have been found to generate Ca2+ sparks--small localized, transient releases from RyRs. The sparks are enhanced by caffeine and blocked by emptying the SR. In rat cells Ca2+ puffs occur in response to agonists, representing the opening of InsP3Rs. The puffs can be abolished by heparin or store emptying. These SR Ca2+-release events affect the excitability of the ureteric cells. In guinea-pig cells, spontaneous transient outward currents (STOCs) can be recorded in response to caffeine application (an agonist for RyR), followed by a shortening of the plateau phase of the action potential. This in turn causes a decrease in the amplitude and duration of the contractions of the ureter. If the SR is inhibited then STOCs are abolished, the action potential plateau prolonged and force increased. Thus it is concluded that the SR acts to limit contraction in the guinea-pig ureter. The mechanism underlying this involves its Ca2+ release being directed to Ca2+-activated K+ channels on the surface membrane and causing STOCs and hyperpolarization, and controlling the duration of the action potential. In rat ureter IICR acts to potentiate force via membrane depolarization and increased L-type Ca2+ entry into the cells. Thus the SR can alter cell signalling and excitation-contraction coupling in the ureter, but its precise role is species dependent. The ureter, with its species-dependent expression of either IICR or CICR provides an ideal system (a natural transgenic model) for studying the SR. Eventually, we will be able to apply this knowledge to the human ureter, to increase our understanding of its functioning in health and disease.

Action Potentials↗

PubMed2002

Role of the sarcoplasmic reticulum in uterine smooth muscle.

The sarcoplasmic reticulum (SR) is present as an extensive network in uterine cells. In this chapter we examine its functional importance, relating in particular, to the control of contractility in pregnancy. The uterine SR has both ryanodine receptors (RyR) and inositol-1 ,4,5-trisphosphate InsP3 receptors (InsP3R). The RyR and subsequent Ca24-induced Ca2+ release play little role in either human or rat contractions or Ca2+ transients. There may be subtle, spatiotemporal effects at the single cell level. Caffeine, an agonist for RyR fails to release Ca2+ and indeed produces relaxation not contraction. InsP3 dearly causes release of Ca2+ from the uterine SR and an increase in force, although these changes are only small and transient compared to those occurring due to external Ca2+ entry. Inhibition of the SR Ca-ATPase by cyclopiazonic acid, empties Ca2+ from the SR. This is associated with an augmentation of force and Ca2+ transient. Thus the SR normally functions in the uterus to limit, not increase contractions. The mechanism may involve vectoral release of Ca2+ from the SR and activation of surface membrane K+ channels. This activation would tend to decrease L-type Ca2+ entry and hence reduce contraction. Thus the SR is playing a role in controlling membrane excitability and hence contractility. The SR also plays a role in the relaxation of force. This is not primarily due to a direct sequestering of large amounts of Ca2+, but rather that the SR directs Ca2+ to the surface membrane extrusion mechanisms, i.e. Ca-ATPase and Na+/Ca2+ exchanger. This enables them to act more efficiently, and therefore aids relaxation. Recent direct measurements of SR luminal content show decreases with agonist application but not during spontaneous activity; confirming the results described above. This technique will be used to better characterize the uterine SR, its control and relevance to normal and abnormal labours.

Animals↗

PubMedDate not supplied

Calcium signalling in smooth muscle.

Calcium signalling in smooth muscles is complex, but our understanding of it has increased markedly in recent years. Thus, progress has been made in relating global Ca2+ signals to changes in force in smooth muscles and understanding the biochemical and molecular mechanisms involved in Ca2+ sensitization, i.e. altering the relation between Ca2+ and force. Attention is now focussed more on the role of the internal Ca2+ store, the sarcoplasmic reticulum (SR), global Ca2+ signals and control of excitability. Modern imaging techniques have shown the elaborate SR network in smooth muscles, along with the expression of IP3 and ryanodine receptors. The role and cross-talk between these two Ca(2+) release mechanisms, as well as possible compartmentalization of the SR Ca2+ store are discussed. The close proximity between SR and surface membrane has long been known but the details of this special region to Ca2+ signalling and the role of local sub-membrane Ca2+ concentrations and membrane microdomains are only now emerging. The activation of K+ and Cl- channels by local Ca2+ signals, can have profound effects on excitability and hence contraction. We examine the evidence for both Ca2+ sparks and puffs in controlling ion channel activity, as well as a fundamental role for Ca2+ sparks in governing the period of inexcitability in smooth muscle, i.e. the refractory period. Finally, the relation between different Ca2+ signals, e.g. sparks, waves and transients, to smooth muscle activity in health and disease is becoming clearer and will be discussed.

Animals↗