Lysosomal agents inhibit store-operated Ca2+ entry

Pharmacological manipulation of lysosome membrane integrity or ionic movements is a key strategy for probing lysosomal involvement in cellular processes. However, we have found an unexpected inhibition of store-operated Ca2+ entry (SOCE) by these agents. Dipeptides (GPN and LLOMe) that are inducers of lysosomal membrane permeabilization (LMP) uncoupled ER Ca2+-store depletion from SOCE by interfering with Stim1 oligomerization and/or Stim1 activation of Orai. Similarly, the K+/H+ ionophore, nigericin, that rapidly elevates lysosomal pH, also inhibited SOCE in a Stim1-dependent manner. In contrast, other strategies for manipulating lysosomes (bafilomycin A1, lysosomal re-positioning) had no effect upon SOCE. Finally, the effects of GPN on SOCE and Stim1 was reversed by a dynamin inhibitor, dynasore. Our data show that lysosomal agents not only release Ca2+ from stores but also uncouple this release from the normal recruitment of Ca2+ influx.

Designing artificial sodium ion reservoirs to emulate biological synapses

Emulating neurons/synapses in the brain is an important step to realizing highly efficient computers. This fact makes neuromorphic devices important emerging solutions to the limitations imposed by the current computing architecture. To mimic synaptic functions in the brain, it is critical to replicate ionic movements in the nervous system. It is therefore important to note that ions move easily in liquids. In this study, we demonstrate a liquid-based neuromorphic device that is capable of mimicking the movement of ions in the nervous system by controlling Na+ movement in an aqueous solution. The concentration of Na+ in the solution can control the ionic conductivity of the device. The device shows short-term and long-term plasticity such as excitatory postsynaptic current, paired-pulse facilitation, potentiation, and depression, which are key properties for memorization and computation in the brain. This device has the potential to overcome the limitations of current von Neumann architecture-based computing systems and substantially advance the technology of neuromorphic computing.

Deregulation of apoptotic volume decrease and ionic movements in multidrug-resistant tumor cells: role of chloride channels

Changes in cell volume and ion gradients across the plasma membrane play a pivotal role in the initiation of apoptosis. Here we explore the kinetics of apoptotic volume decrease (AVD) and ion content dynamics in wild-type (WT) and multidrug-resistant (MDR) Ehrlich ascites tumor cells (EATC). In WT EATC, induction of apoptosis with cisplatin (5 μM) leads to three distinctive AVD stages: an early AVD1 (4–12 h), associated with a 30% cell water loss; a transition stage AVDT (∼12 to 32 h), where cell volume is partly recovered; and a secondary AVD2 (past 32 h), where cell volume was further reduced. AVD1 and AVD2 were coupled to net loss of Cl−, K+, Na+, and amino acids (ninhydrin-positive substances), whereas during AVDT, Na+ and Cl− were accumulated. MDR EATC was resistant to cisplatin, showing increased viability and less caspase 3 activation. Compared with WT EATC, MDR EATC underwent a less pronounced AVD1, an augmented AVDT, and a delay in induction of AVD2. Changes in AVD were associated with inhibition of Cl− loss during AVD1, augmented NaCl uptake during AVDT, and a delay of Cl− loss during AVD2. Application of the anion channel inhibitor NS3728 inhibited AVD and completely abolished the differences in AVD, ionic movements, and caspase 3 activation between WT and MDR EATC. Finally, the maximal capacity of volume-regulated anion channel was found to be strongly repressed in MDR EATC. Together, these data suggest that impairment of AVD, primarily via modulation of NaCl movements, contribute to protection against apoptosis in MDR EATC.

INSECT ION HOMEOSTASIS.

The constant composition of body fluids in insects is maintained by the cooperative interaction of gastrointestinal and urinary tissues. Water follows ionic movements, which are driven by the basolateral Na+/K+-ATPase and/or the apical 'K+(or Na+) pump'. The latter now is thought to be the functional expression of a parallel arrangement of a proton-motive V-ATPase and a K+(or Na+)/nH+ antiport. This review focuses on the pathways for the movement of monovalent inorganic ions through epithelia involved in ion homeostasis. A graphical summary compares the principal findings with respect to cation secretion in lepidopteran caterpillar midgut goblet cells (K+) and in brush-border cells of Malpighian tubules (K+, Na+).