Mitochondrial control of calcium-channel gating: A mechanism for sustained signaling and transcriptional activation in T lymphocytes

In addition to their well-known functions in cellular energy transduction, mitochondria play an important role in modulating the amplitude and time course of intracellular Ca2+ signals. In many cells, mitochondria act as Ca2+ buffers by taking up and releasing Ca2+, but this simple buffering action by itself often cannot explain the organelle's effects on Ca2+ signaling dynamics. Here we describe the functional interaction of mitochondria with store-operated Ca2+ channels in T lymphocytes as a mechanism of mitochondrial Ca2+ signaling. In Jurkat T cells with functional mitochondria, prolonged depletion of Ca2+ stores causes sustained activation of the store-operated Ca2+ current, ICRAC (CRAC, Ca2+ release-activated Ca2+). Inhibition of mitochondrial Ca2+ uptake by compounds that dissipate the intramitochondrial potential unmasks Ca2+-dependent inactivation of ICRAC. Thus, functional mitochondria are required to maintain CRAC-channel activity, most likely by preventing local Ca2+ accumulation near sites that govern channel inactivation. In cells stimulated through the T-cell antigen receptor, acute blockade of mitochondrial Ca2+ uptake inhibits the nuclear translocation of the transcription factor NFAT in parallel with CRAC channel activity and [Ca2+]i elevation, indicating a functional link between mitochondrial regulation of ICRAC and T-cell activation. These results demonstrate a role for mitochondria in controlling Ca2+ channel activity and signal transmission from the plasma membrane to the nucleus.

Increased Activation of Stromal Interaction Molecule-1/Orai-1 in Aorta From Hypertensive Rats A Novel Insight Into Vascular Dysfunction

Disturbances in the regulation of cytosolic calcium (Ca(2+)) concentration play a key role in the vascular dysfunction associated with arterial hypertension. Stromal interaction molecules (STIMs) and Orai proteins represent a novel mechanism to control store-operated Ca(2+) entry. Although STIMs act as Ca(2+) sensors for the intracellular Ca(2+) stores, Orai is the putative pore-forming component of Ca(2+) release-activated Ca(2+) channels at the plasma membrane. We hypothesized that augmented activation of Ca(2+) release-activated Ca(2+)/Orai-1, through enhanced activity of STIM-1, plays a role in increased basal tonus and vascular reactivity in hypertensive animals. Endothelium-denuded aortic rings from Wistar-Kyoto and stroke-prone spontaneously hypertensive rats were used to evaluate contractions because of Ca(2+) influx. Depletion of intracellular Ca(2+) stores, which induces Ca(2+) release-activated Ca(2+) activation, was performed by placing arteries in Ca(2+) free-EGTA buffer. The addition of the Ca(2+) regular buffer produced greater contractions in aortas from stroke-prone spontaneously hypertensive rats versus Wistar-Kyoto rats. Thapsigargin (10 mu mol/L), an inhibitor of the sarcoplasmic reticulum Ca(2+) ATPase, further increased these contractions, especially in stroke-prone spontaneously hypertensive rat aorta. Addition of the Ca(2+) release-activated Ca(2+) channel inhibitors 2-aminoethoxydiphenyl borate (100 mu mol/L) or gadolinium (100 mu mol/L), as well as neutralizing antibodies to STIM-1 or Orai-1, abolished thapsigargin-increased contraction and the differences in spontaneous tone between the groups. Expression of Orai-1 and STIM-1 proteins was increased in aorta from stroke-prone spontaneously hypertensive rats when compared with Wistar-Kyoto rats. These results support the hypothesis that both Orai-1 and STIM-1 contribute to abnormal vascular function in hypertension. Augmented activation of STIM-1/Orai-1 may represent the mechanism that leads to impaired control of intracellular Ca(2+) levels in hypertension. (Hypertension. 2009; 53[part 2]: 409-416.)

Micropolar flow in a porous channel with high mass transfer

Two dimensional flow of a micropolar fluid in a porous channel is investigated. The flow is driven by suction or injection at the channel walls, and the micropolar model due to Eringen is used to describe the working fluid. An extension of Berman's similarity transform is used to reduce the governing equations to a set of non-linear coupled ordinary differential equations. The latter are solved for large mass transfer via a perturbation analysis where the inverse of the cross-flow Reynolds number is used as the perturbing parameter. Complementary numerical solutions for strong injection are also obtained using a quasilinearisation scheme, and good agreement is observed between the solutions obtained from the perturbation analysis and the computations.

Pedestrians Effects on Indoor MIMO-OFDM Channel Capacity

Temporal variations caused by pedestrian movement can significantly affect the channel capacity of indoor MIMOOFDM wireless systems. This paper compares systematic measurements of MIMO-OFDM channel capacity in presence of pedestrians with predicted MIMO-OFDM channel capacity values using geometric optics-based ray tracing techniques. Capacity results are presented for a single room environment using 5.2 GHz with 2x2, 3x3 and 4x4 arrays as well as a 2.45 GHz narrowband 8x8 MIMO array. The analysis shows an increase of up to 2 b/s/Hz on instant channel capacity with up to 3 pedestrians. There is an increase of up to 1 b/s/Hz in the average capacity of the 4x4 MIMO-OFDM channel when the number of pedestrians goes from 1 to 3. Additionally, an increment of up to 2.5 b/s/Hz in MIMO-OFDM channel capacity was measured for a 4x4 array compared to a 2x2 array in presence of pedestrians. Channel capacity values derived from this analysis are important in terms of understanding the limitations and possibilities for MIMO-OFDM systems in indoor populated environments.