TRPC1 channels regulate directionality of migrating cells.

Cell migration depends on the generation of structural asymmetry and on different steps: protrusion and adhesion at the front and traction and detachment at the rear part of the cell. The activity of Ca(2+) channels coordinate these steps by arranging intracellular Ca(2+) signals along the axis of movement. Here, we investigated the role of the putative mechanosensitive canonical transient receptor potential channel 1 (TRPC1) in cell migration. We analyzed its function in transformed renal epithelial (Madin-Darby canine kidney-focus) cells with variation of TRPC1 expression. As shown by time lapse video microscopy, TRPC1 knockdown cells have partially lost their polarity and the ability to persistently migrate into a given direction. This failure is linked to the suppression of a local Ca(2+) gradient at the front of migrating TRPC1 knockdown cells, whereas TRPC1 overexpression leads to steeper Ca(2+) gradients. We propose that the Ca(2+) signaling events regulated by TRPC1 within the lamellipodium determine polarity and directed cell migration.

A novel function of capsaicin-sensitive TRPV1 channels: involvement in cell migration.

Cell migration relies on a tight temporal and spatial regulation of the intracellular Ca2+ concentration ([Ca2+]i). [Ca2+]i in turn depends on Ca2+ influx via channels in the plasma membrane whose molecular nature is still largely unknown for migrating cells. A mechanosensitive component of the Ca2+ influx pathway was suggested. We show here that the capsaicin-sensitive transient receptor potential channel TRPV1, that plays an important role in pain transduction, is one of the Ca2+ influx channels involved in cell migration. Activating TRPV1 channels with capsaicin leads to an acceleration of human hepatoblastoma (HepG2) cells pretreated with hepatocyte growth factor (HGF). The speed rises by up to 50% and the displacement is doubled. Patch clamp experiments revealed the presence of capsaicin and resiniferatoxin (RTX)-sensitive currents. In contrast, HepG2 cells kept in the absence of HGF are not accelerated by capsaicin and express no capsaicin- or RTX-sensitive current. The TRPV1 antagonist capsazepine prevents the stimulation of migration and inhibits capsaicin-sensitive currents. Finally, we compared the contribution of capsaicin-sensitive TRPV1 channels to cell migration with that of mechanosensitive TRPV4 channels that are also expressed in HepG2 cells. A specific TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate, does not increase the displacement. In summary, we assigned a novel role to capsaicin-sensitive TRPV1 channels. They are important Ca2+ influx channels required for cell migration.

Prehospital determination of tracheal tube placement in severe head injury.

OBJECTIVES: The aim of this prospective study in the prehospital setting was to compare three different methods for immediate confirmation of tube placement into the trachea in patients with severe head injury: auscultation, capnometry, and capnography. METHODS: All adult patients (>18 years) with severe head injury, maxillofacial injury with need of protection of airway, or polytrauma were intubated by an emergency physician in the field. Tube position was initially evaluated by auscultation. Then, capnometry and capnography was performed (infrared method). Emergency physicians evaluated capnogram and partial pressure of end tidal carbon dioxide (EtCO(2)) in millimetres of mercury. Determination of final tube placement was performed by a second direct visualisation with laryngoscope. Data are mean (SD) and percentages. RESULTS: There were 81 patients enrolled in this study (58 with severe head injury, 6 with maxillofacial trauma, and 17 politraumatised patients). At the first attempt eight patients were intubated into the oesophagus. Afterwards endotracheal intubation was undertaken in all without complications. The initial capnometry (sensitivity 100%, specificity 100%), capnometry after sixth breath (sensitivity 100%, specificity 100%), and capnography after sixth breath (sensitivity 100%, specificity 100%) were significantly better indicators for tracheal tube placement than auscultation (sensitivity 94%, specificity 66%, p<0.01). CONCLUSION: Auscultation alone is not a reliable method to confirm endotracheal tube placement in severely traumatised patients in the prehospital setting. It is necessary to combine auscultation with other methods like capnometry or capnography.