Dissecting Cellular Mechanisms of Long-Chain Acylcarnitines-Driven Cardiotoxicity: Disturbance of Calcium Homeostasis, Activation of Ca-Dependent Phospholipases, and Mitochondrial Energetics Collapse.

Long-chain acylcarnitines (LCAC) are implicated in ischemia-reperfusion (I/R)-induced myocardial injury and mitochondrial dysfunction. Yet, molecular mechanisms underlying involvement of LCAC in cardiac injury are not sufficiently studied. It is known that in cardiomyocytes, palmitoylcarnitine (PC) can induce cytosolic Ca accumulation, implicating L-type calcium channels, Na/Ca exchanger, and Ca-release from sarcoplasmic reticulum (SR).

NMDA receptor modulation of glutamate release in activated neutrophils.

Background: Neutrophil depletion improves neurologic outcomes in experimental sepsis/brain injury. We hypothesized that neutrophils may exacerbate neuronal injury through the release of neurotoxic quantities of the neurotransmitter glutamate.

Methods: Real-time glutamate release by primary human neutrophils was determined using enzymatic biosensors.

Mechanisms of CO2/H+ Sensitivity of Astrocytes.

Unlabelled: Ventral regions of the medulla oblongata of the brainstem are populated by astrocytes sensitive to physiological changes in P/[H]. These astrocytes respond to decreases in pH with elevations in intracellular Ca and facilitated exocytosis of ATP-containing vesicles. Released ATP propagates Ca excitation among neighboring astrocytes and activates neurons of the brainstem respiratory network triggering adaptive increases in breathing.

Astrocytes and Brain Hypoxia.

Astrocytes provide the structural and functional interface between the cerebral circulation and neuronal networks. They enwrap all intracerebral arterioles and capillaries, control the flux of nutrients as well as the ionic and metabolic environment of the neuropil. Astrocytes have the ability to adjust cerebral blood flow to maintain constant PO2 and PCO2 of the brain parenchyma.

Functional Oxygen Sensitivity of Astrocytes.

In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short period of time. However, oxygen tension monitored by the peripheral (arterial) chemoreceptors is not sensitive to regional CNS differences in partial pressure of oxygen (PO2 ) that reflect variable levels of neuronal activity or local tissue hypoxia, pointing to the necessity of a functional brain oxygen sensor. This experimental animal (rats and mice) study shows that astrocytes, the most numerous brain glial cells, are sensitive to physiological changes in PO2 .