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Aberrant functioning of the proteasome has been associated with crucial pathologic conditions including neurodegeneration. Yet, the complex underlying causes at the cellular level remain unclear and there are conflicting reports of neuroprotective to neurodegenerative effects of proteasomal inhibitors such as lactacystin that are utilised as models for neurodegenerative diseases. The conflicting results may be associated with different dose regimes of lactacystin and hence we have performed a dose dependent study of the effects of lactacystin to identify concurrent changes in the cell membrane lipid profile and the dynamics of exocytosis using a combination of surface sensitive mass spectrometry and single cell amperometry. Significant changes of negatively charged lipids were associated with different lactacystin doses that showed a weak correlation with exocytosis while changes in PE and PE−O lipids showed dose dependent changes correlated with initial pore formation and total release of vesicle content respectively. [ABSTRACT FROM AUTHOR]

Aberrant functioning of the proteasome has been associated with crucial pathologic conditions including neurodegeneration. Yet, the complex underlying causes at the cellular level remain unclear and there are conflicting reports of neuroprotective to neurodegenerative effects of proteasomal inhibitors such as lactacystin that are utilised as models for neurodegenerative diseases. The conflicting results may be associated with different dose regimes of lactacystin and hence we have performed a dose dependent study of the effects of lactacystin to identify concurrent changes in the cell membrane lipid profile and the dynamics of exocytosis using a combination of surface sensitive mass spectrometry and single cell amperometry. Significant changes of negatively charged lipids were associated with different lactacystin doses that showed a weak correlation with exocytosis while changes in PE and PE−O lipids showed dose dependent changes correlated with initial pore formation and total release of vesicle content respectively. [ABSTRACT FROM AUTHOR]

The dopaminergic system has been suggested to serve as a functional target for ketamine, especially with its addictive and antidepressant effects. In this work, intracellular vesicle impact electrochemical cytometry and single cell amperometry were applied to a model cell line to show that the intravesicular contents and number of exocytotic events increased and the fraction of release decreased after treatment by subanesthetic ketamine (1 μM for 15 min). In addition, time‐of‐flight secondary ion mass spectrometry was used to show that cellular lipids change following acute ketamine administration relative to control cells with an increased proportion of low‐curvature lipids and a decreased proportion of high‐curvature lipids. We propose that ketamine modulates dopaminergic function with a dose‐dependent pharmacologic action by dominantly interacting with different proteins and changing lipid composition. It might be helpful to better understand the relationship of the dopaminergic system and drug abuse, as well as anesthetic and antidepressant effects. [ABSTRACT FROM AUTHOR]