br Some general considerations on
Some general considerations on anterior pituitary cell type, models, sex and drugs Historically, real-time analysis of native endocrine anterior pituitary cell excitability has been somewhat limited and thus much of the pioneering work on anterior pituitary cell excitability and stimulus-secretion coupling was elucidated with a variety of immortalized clonal cell lines that retain some, but not all, properties of native DCA australia (Ooi et al., 2004). Indeed, several differences in excitability and regulation between clonal cell lines and native cells are well known. For example, variants of the mouse corticotroph cell line AtT20 lack receptors for the major secretagogue AVP, but it is perhaps not surprising to find such differences when these lines were derived from pituitary tumours derived from mice exposed to an atomic bomb! In general, isolation of distinct pituitary cell types has remained a challenge and the vast majority of work has been undertaken on primary dispersed cells in short term culture with cellular identification determined by responses to hypothalamic secretagogues. A number of recent studies have begun to exploit mouse models in which specific cell types are genetically labelled with fluorescent proteins – either as transgenes or using viral transduction with fluorescent protein expression driven by cell specific promoters (Duncan et al., 2015, Duncan et al., 2016, Fletcher et al., 2017, Liang et al., 2011, Romanò et al., 2017, Zemkova et al., 2016). These data have begun to provide valuable insights into basal/spontaneous activity in the absence of secretagogue and allow a clearer examination of heterogeneity of responsiveness among pituitary cell populations. However, there are also several broader considerations to take into account when analyzing anterior pituitary cell excitability, that are further highlighted in section 4, including:
Calcium-activated potassium channels and control of anterior pituitary excitability
Conclusions & perspectives The family of calcium-activated potassium channels clearly play an important and diverse role in controlling electrical excitability of anterior pituitary endocrine cells. Importantly, these roles are both cell- and context-specific with calcium-activated channels playing some unexpected roles beyond their ‘classical’ contribution to calcium-dependent repolarization and decrease in membrane excitability observed in many other excitable cells. However, while we are starting to understand some of the physiological functions of BK, SK and IK channels in anterior pituitary endocrine function many outstanding questions remain that represent a major challenge for the field including:
Acknowledgements This work was generously supported by a Medical Research Council grant (Ref: MR/J008893/1) to MJS.
Introduction High hemoglobin content and continual contact with oxygen unavoidably result in the formation of reactive oxygen species (ROS) in erythrocytes , . In addition, in the body, erythrocytes are attacked by exogenous ROS, originating from other blood cells (platelets, neutrophils, monocytes, and macrophages) and vessel endothelium , , as well as from certain xenobyotics and medicines , . Physiological erythrocyte aging and sequestration of senescent cells are thought to be due to oxidative damage accumulated in erythrocytes over their lifespan in the circulation (about 120 days) . In the norm, the endogenous antioxidant defense system provides for the balance between ROS generation and scavenging. In various disease conditions (certain enzymo- and hemoglobinopathies, inflammation, sepsis, ischemia–reperfusion, shock, and burns), the balance of ROS production and degradation is impaired, resulting in the so-called “oxidative stress”. Clinical efficacy of antioxidants and cytotoxic drugs cannot be achieved without a detailed understanding of the mechanisms by which ROS affect cells and subcellular structures. This line of research has been extensively pursued over the last decades.