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Astrocyte store-operated Ca2+ entry controls gliotransmitter release to alter hippocampal excitability. A CRAC team for astrocytes: Astrocytes are the most abundant glial cell type in the brain and release small molecules in a Ca2+-dependent fashion, such as ATP, that regulate neuronal excitability. Toth et al. found that Ca2+ release–activated Ca2+ (CRAC) channels comprising the Ca2+ sensor STIM1 and the Ca2+ channel Orai1 were a major route of Ca2+ entry into hippocampal astrocytes. Genetic ablation of either STIM1 or Orai1 in astrocytes decreased intracellular Ca2+ increases in response to the purinergic receptor agonists ATP or UTP or the protease-activated receptor agonist thrombin. Furthermore, astrocytes deficient in Orai1 showed reduced vesicle exocytosis and ATP release, as well as an inability to stimulate the excitability of hippocampal interneurons. These results suggest that enhancing CRAC channel activity in astrocytes could be a strategy to suppress neuronal excitability. Astrocytes are the major glial subtype in the brain and mediate numerous functions ranging from metabolic support to gliotransmitter release through signaling mechanisms controlled by Ca2+. Despite intense interest, the Ca2+ influx pathways in astrocytes remain obscure, hindering mechanistic insights into how Ca2+ signaling is coupled to downstream astrocyte-mediated effector functions. Here, we identified store-operated Ca2+ release–activated Ca2+ (CRAC) channels encoded by Orai1 and STIM1 as a major route of Ca2+ entry for driving sustained and oscillatory Ca2+ signals in astrocytes after stimulation of metabotropic purinergic and protease-activated receptors. Using synaptopHluorin as an optical reporter, we showed that the opening of astrocyte CRAC channels stimulated vesicular exocytosis to mediate the release of gliotransmitters, including ATP. Furthermore, slice electrophysiological recordings showed that activation of astrocytes by protease-activated receptors stimulated interneurons in the CA1 hippocampus to increase inhibitory postsynaptic currents on CA1 pyramidal cells. These results reveal a central role for CRAC channels as regulators of astrocyte Ca2+ signaling, gliotransmitter release, and astrocyte-mediated tonic inhibition of CA1 pyramidal neurons. [ABSTRACT FROM AUTHOR]

Background: The clinical importance of the right ventricle (RV) has recently been recognized; however, assessing its function during cardiac surgery remains challenging owing to its complex anatomy. A temporary transvenous pacing catheter is a useful tool in the small surgical field of minimally invasive cardiac surgery, and an electrocardiogram recorded through the catheter is composed of the direct electrophysiological activity of the RV. Therefore, we hypothesized that QRS duration in the RV (QRS RV ) could be a useful monitoring parameter for perioperative RV function., Methods: We conducted a prospective cohort analysis involving adult patients undergoing robotic mitral valve repair. A bipolar pacing catheter was inserted using x-ray fluoroscopy, and the QRS RV duration was assessed at four time points: preoperative baseline, during one-lung ventilation, after weaning from cardiopulmonary bypass, and before the end of surgery. At the same time points, right ventricular fractional area change (RVFAC) measured by transesophageal echocardiography and QRS duration at V5 lead of the body surface electrocardiogram (QRS V5 ) were also evaluated., Results: In the 94 patients analyzed, QRS RV duration was significantly prolonged during robotic mitral valve repair ( p  = 0.0009), whereas no significant intraoperative changes in RVFAC were observed ( p  = 0.2). By contrast, QRS V5 duration was significantly shortened during surgery ( p  < 0.00001). Multilinear regression showed a significant correlation of QRS RV duration with RVFAC ( p  = 0.00006), but not with central venous pressure ( p  = 0.9), or left ventricular ejection fraction ( p  = 0.3). When patients were divided into two groups by postoperative QRS RV  > 100 or ≤100 ms, 25 patients (26.6%) exhibited the prolonged QRS RV duration, and the mean increase in the postoperative QRS RV from preoperative baseline was 12 ms ( p  = 0.001), which was only 0.6 ms in patients with QRS RV  ≤ 100 ms ( p  = 0.6). Cox regression analysis showed that prolonged postoperative QRS RV duration was the only significant parameter associated with a longer ICU stay after surgery ( p  = 0.02; hazard ratio, 0.55)., Conclusion: Our data suggest that QRS RV duration is a useful parameter for monitoring the RV during cardiac surgery, possibly better than a commonly used echocardiographic parameter, RVFAC. An electrophysiological assessment by QRS RV duration could be a practical tool for the complex anatomy of the RV, especially with limited modalities in perioperative settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Watanabe, Hori, Ishihara, Tsujikawa, Hino, Matsuura, Takahashi, Shibata and Mori.)

An 82-year-old man underwent thoracoscopic upper lobectomy of the left lung for the treatment of the lung cancer. The major complication was asymptomatic chronic trifascicular block. During the surgery, after the upper lobe had been resected, second degree atrioventricular block (Morbitz type II) occurred unexpectedly, soon evolving in complete AV block, with pulse wave disappearing, indicating pulseless electrical activity. Immediately, we used an epicardial pacing wire, and spontaneous circulation returned. Postoperatively, a permanent pacemaker was implanted. Asymptomatic chronic bifascicular block and trifascicular block rarely progress into complete AV block during operation, which we should be prepared in advance. Accordingly in some cases, preoperative insertion of a temporary pacemaker should be considered as a preventive measure.