Cytoplasmic Ca2+ oscillations evoked by acetylcholine or intracellular infusion of inositol trisphosphate or Ca2+ can be inhibited by internal Ca2+

AbstractIn single internally perfused mouse pancreatic acinar cells, changes in the free intracellular Ca2+ concentration ([Ca2+]i) were monitored by measuring the Ca2+-dependent transmembrane Cl− current under voltage-clamp conditions. Cytoplasmic Ca2+ oscillations were induced by external acetylcholine (ACh) application, internal infusion of inositol (1,4,5) trisphosphate or its non-metabolizable analogue inositol trisphosphorothioate or by intracellular Ca2+ infusion. Such [Ca2+]i oscillations could be rapidly inhibited by external application of the Ca2+ ionophore ionomycin (10–100 nM). Cytoplasmic Ca2+ oscillations could also be evoked by external caffeine (1 mM) application when the internal perfusion solution did not contain any Ca2+ chelator. In such cases intracellular Ca2+ infusion transiently abolished the [Ca2+]i oscillations. We conclude that although Ca2+-induced Ca2+ release is the cause of the ACh-evoked [Ca2+]i oscillations, there is also a negative feed-back since Ca2+ can inhibit Ca2+ release initiated by Ca2+

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Ca2+ signaling in pancreatic acinar cells: physiology and pathophysiology

The pancreatic acinar cell is a classical model for studies of secretion and signal transduction mechanisms. Because of the extensive endoplasmic reticulum and the large granular compartment, it has been possible - by direct measurements - to obtain considerable insights into intracellular Ca2+ handling under both normal and pathological conditions. Recent studies have also revealed important characteristics of stimulus-secretion coupling mechanisms in isolated human pancreatic acinar cells. The acinar cells are potentially dangerous because of the high intra-granular concentration of proteases, which become inappropriately activated in the human disease acute pancreatitis. This disease is due to toxic Ca2+ signals generated by excessive liberation of Ca2+ from both the endoplasmic reticulum and the secretory granules

Single-channel Ba2+ currents in insulin-secreting cells are activated by glyceraldehyde stimulation

AbstractSingle-channel Ba2+ current recordings have been made from the insulin-secreting cell line RINm5F with the patch-clamp technique. Depolarization evokes opening of Ca2+ (Ba2+) channels with a relatively high conductance (30 pS) and during the 200 ms depolarizing pulses there is no inactivation. The threshold is high as 50 mV depolarization from the resting membrane potential of −70 mV is required for any channel opening to occur. Glyceraldehyde, a substance evoking insulin secretion from the RINm5F cells, enhances the voltage-activated Ca2+ channel opening by increasing the mean open time and decreasing the longer of the two mean shut times and also decreases the voltage threshold for channel opening

Neuronal calcium stores

Neuronal calcium stores associated with specialized intracellular organelles, such as endoplasmic reticulum and mitochondria, dynamically participate in generation of cytoplasmic calcium signals which accompany neuronal activity. They fulfil a dual role in neuronal Ca2+ homeostasis being involved in both buffering the excess of Ca2+ entering the cytoplasm through plasmalemmal channels and providing an intracellular source for Ca2+. Increase of Ca2+ content within the stores regulates the availability and magnitude of intracellular calcium release, thereby providing a mechanism which couples the neuronal activity with functional state of intracellular Ca2+ stores. Apart of 'classical' calcium stores (endoplasmic reticulum and mitochondria) other organelles (e.g. nuclear envelope and neurotransmitter vesicles) may potentially act as a functional Ca2+ storage compartments. Calcium ions released from internal stores participate in many neuronal functions, and might be primarily involved in regulation of various aspects of neuronal plasticity