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Physiological Reviews Oct 2023Calcium signaling underlies much of physiology. Almost all the Ca in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels... (Review)
Review
Calcium signaling underlies much of physiology. Almost all the Ca in the cytoplasm is bound to buffers, with typically only ∼1% being freely ionized at resting levels in most cells. Physiological Ca buffers include small molecules and proteins, and experimentally Ca indicators will also buffer calcium. The chemistry of interactions between Ca and buffers determines the extent and speed of Ca binding. The physiological effects of Ca buffers are determined by the kinetics with which they bind Ca and their mobility within the cell. The degree of buffering depends on factors such as the affinity for Ca, the Ca concentration, and whether Ca ions bind cooperatively. Buffering affects both the amplitude and time course of cytoplasmic Ca signals as well as changes of Ca concentration in organelles. It can also facilitate Ca diffusion inside the cell. Ca buffering affects synaptic transmission, muscle contraction, Ca transport across epithelia, and the killing of bacteria. Saturation of buffers leads to synaptic facilitation and tetanic contraction in skeletal muscle and may play a role in inotropy in the heart. This review focuses on the link between buffer chemistry and function and how Ca buffering affects normal physiology and the consequences of changes in disease. As well as summarizing what is known, we point out the many areas where further work is required.
Topics: Humans; Calcium; Buffers; Cytoplasm; Heart; Synaptic Transmission; Calcium Signaling
PubMed: 37326298
DOI: 10.1152/physrev.00042.2022 -
The Journal of Emergency Medicine Aug 2023The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy. (Review)
Review
BACKGROUND
The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy.
OBJECTIVE
In this narrative review, we describe the physiology behind commonly encountered nontoxicologic causes of metabolic acidosis, highlight potential harm from the indiscriminate administration of sodium bicarbonate in certain scenarios, and provide evidence-based recommendations to assist emergency physicians in the rational use of sodium bicarbonate.
DISCUSSION
Sodium bicarbonate can be administered as a hypertonic push, as a resuscitation fluid, or as an infusion. Lactic acidosis and cardiac arrest are two common scenarios where there is limited benefit to routine use of sodium bicarbonate, although certain circumstances, such as patients with concomitant acute kidney injury and lactic acidosis may benefit from sodium bicarbonate. Patients with cardiac arrest secondary to sodium channel blockade or hyperkalemia also benefit from sodium bicarbonate therapy. Recent data suggest that the use of sodium bicarbonate in diabetic ketoacidosis does not confer improved patient outcomes and may cause harm in pediatric patients. Available evidence suggests that alkalinization of urine in rhabdomyolysis does not improve patient-centered outcomes. Finally, patients with a nongap acidosis benefit from sodium bicarbonate supplementation.
CONCLUSIONS
Empiric use of sodium bicarbonate in patients with nontoxicologic causes of metabolic acidosis is not warranted and likely does not improve patient-centered outcomes, except in select scenarios. Emergency physicians should reserve use of this medication to conditions with clear benefit to patients.
Topics: Humans; Child; Bicarbonates; Sodium Bicarbonate; Acidosis, Lactic; Acidosis; Heart Arrest
PubMed: 37442665
DOI: 10.1016/j.jemermed.2023.04.012 -
Neuron Dec 2023Understanding how individuals form and maintain strong social networks has emerged as a significant public health priority as a result of the increased focus on the... (Review)
Review
Understanding how individuals form and maintain strong social networks has emerged as a significant public health priority as a result of the increased focus on the epidemic of loneliness and the myriad protective benefits conferred by social connection. In this review, we highlight the psychological and neural mechanisms that enable us to connect with others, which in turn help buffer against the consequences of stress and isolation. Central to this process is the experience of rewards derived from positive social interactions, which encourage the sharing of perspectives and preferences that unite individuals. Sharing affective states with others helps us to align our understanding of the world with another's, thereby continuing to reinforce bonds and strengthen relationships. These psychological processes depend on neural systems supporting reward and social cognitive function. Lastly, we also consider limitations associated with pursuing healthy social connections and outline potential avenues of future research.
Topics: Humans; Emotions; Cognition; Reward
PubMed: 37804834
DOI: 10.1016/j.neuron.2023.09.012 -
Hamostaseologie Feb 2024
Topics: Humans; Sodium Citrate; Blood Platelets
PubMed: 38417800
DOI: 10.1055/s-0044-1782595 -
Nature Nov 2023Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular...
Optimum protein function and biochemical activity critically depends on water availability because solvent thermodynamics drive protein folding and macromolecular interactions. Reciprocally, macromolecules restrict the movement of 'structured' water molecules within their hydration layers, reducing the available 'free' bulk solvent and therefore the total thermodynamic potential energy of water, or water potential. Here, within concentrated macromolecular solutions such as the cytosol, we found that modest changes in temperature greatly affect the water potential, and are counteracted by opposing changes in osmotic strength. This duality of temperature and osmotic strength enables simple manipulations of solvent thermodynamics to prevent cell death after extreme cold or heat shock. Physiologically, cells must sustain their activity against fluctuating temperature, pressure and osmotic strength, which impact water availability within seconds. Yet, established mechanisms of water homeostasis act over much slower timescales; we therefore postulated the existence of a rapid compensatory response. We find that this function is performed by water potential-driven changes in macromolecular assembly, particularly biomolecular condensation of intrinsically disordered proteins. The formation and dissolution of biomolecular condensates liberates and captures free water, respectively, quickly counteracting thermal or osmotic perturbations of water potential, which is consequently robustly buffered in the cytoplasm. Our results indicate that biomolecular condensation constitutes an intrinsic biophysical feedback response that rapidly compensates for intracellular osmotic and thermal fluctuations. We suggest that preserving water availability within the concentrated cytosol is an overlooked evolutionary driver of protein (dis)order and function.
Topics: Cell Death; Cytosol; Homeostasis; Macromolecular Substances; Osmolar Concentration; Pressure; Proteins; Solvents; Temperature; Thermodynamics; Time Factors; Water
PubMed: 37853127
DOI: 10.1038/s41586-023-06626-z -
Acta Neurobiologiae Experimentalis Dec 2023Over the past decade glymphatic concept has gained more and more interest. Despite some lacking data regarding structural and functional aspects, glymphatic system is... (Review)
Review
Over the past decade glymphatic concept has gained more and more interest. Despite some lacking data regarding structural and functional aspects, glymphatic system is widely considered the main mechanism of water and solutes transport in brain parenchyma, as well as waste clearance from the brain. Glymphatic system modulates the extracellular space volume and is involved in spatial K+ buffering (via influencing Kir4.1 channel functioning), two factors crucial for neuronal excitability and seizure susceptibility, and is itself strongly stimulated during sleep. This review summarizes information regarding the potential role of the glymphatic system in the development and progression of epilepsy, especially the role of the glial water channel aquaporin‑4 in modulation of brain excitability and in epilepsy. Data from animal models and human studies are presented.
Topics: Animals; Humans; Brain; Epilepsy; Glymphatic System; Neuroglia; Seizures; Aquaporin 4
PubMed: 38224279
DOI: 10.55782/ane-2023-2498