Thomas Voets. 321-sports-betting.info full professor. head of the Laboratory of Ion Channel Research · mail & phone. Education: Agricultural engineer (KU Leuven). Thomas Voets. photo. mail Show email. Laboratory of Ion Channel Research ( VIB-KU Leuven Center for Brain & Disease Research). O&N I Herestraat 49 - box . Ion channels are protein-based pores present in biological membranes that open and close in response to distinct chemical or physical stimuli (a process known.
The signaling was specific for the pain response to heat, as the animals responded normally to other painful stimuli such as cold, pressure or pinpricks, and their overall thermal preference was not affected. This triple knock out mouse represents the first demonstration in mammals of elimination of the pain response to a physical stimulus at the level of the signal-transducing ion channel.
It ensures we avoid dangerous heat, even if one or even two heat sensors are compromised. In such conditions, the three heat-activated TRP channels can get deregulated, signaling painful heat even when there is no risk of burning.
By developing new drugs that specifically temper the activity of these molecular heat detectors, we hope to be able to provide effective and safe means to treat chronic pain in patients. The realizations of VIB researchers can form the basis of new therapies, but the development path still takes years.
This can raise a lot of questions. That is why we ask you to please refer questions in your report or article to the email address that VIB makes available for this purpose: Interestingly, most residual heat-sensitive neurons in the double knockout mice also responded to allyl isothiocyanate, responsible for the pungent sensation of mustard, radish and wasabi.
This chemical selectively activates a third TRP channel, which prompted the scientists to go one step further and generate a triple knockout. Mice with all three TRP channels eliminated showed a complete loss of heat-induced pain responses. Reintroduction of the receptors via transient transfection restored sensitivity to heat, and conversely, heat responses could also be suppressed by an inhibitor cocktail for all three TRP channels. The signaling was specific for the pain response to heat, as the animals responded normally to other painful stimuli such as cold, pressure or pinpricks, and their overall thermal preference was not affected.
This triple knock out mouse represents the first demonstration in mammals of elimination of the pain response to a physical stimulus at the level of the signal-transducing ion channel. It ensures we avoid dangerous heat, even if one or even two heat sensors are compromised. Functional evidence has been presented that implicate synaptotagmin I in vesicle docking 14 , fusion 15 — 20 , and recycling However, other explanations for the impairment of synchronous release in synaptotagmin I mutants cannot be excluded.
Using these methods, we demonstrate that synaptotagmin I-deficient chromaffin cells display a selective loss of functional readily releasable vesicles. The results are discussed in the framework of our current model for LDCV exocytosis in chromaffin cells. After the electrophysiological recordings, we genotyped newborn mice independently, by using PCR and synaptotagmin I-specific primers.
Whole-cell patch-clamp recordings 24 were performed by using a pipette solution containing mM Cs-glutamate, 8 mM NaCl, 3.
A constant voltage of mV vs. The amperometric current was sampled at 10 kHz and digitally filtered at 1 kHz. Analysis of single spikes was as described The resulting C m increase Fig.
Detailed kinetic analysis of the initial phase of the flash response Fig. The exocytic burst could be fitted by the sum of two exponential terms smooth line in Fig. The fast and slower component correspond to the exocytosis of vesicles from two distinct populations of fusion-competent vesicles: For this control cell, this procedure yielded an RRP size of fF with a fusion rate constant of In contrast to controls, the exocytic burst of mutant cells could be well fitted by a single exponential with, for this example, an amplitude of 86 fF and a fusion rate constant of 6.
B The resulting C m increase consisted of a rapid initial phase exocytic burst followed by a sustained phase. C First ms of the flash response boxed area in B with a double-exponential fit overlaid smooth line. C Inset The first 30 ms after the flash, illustrating the brief delay between the flash arrow and the onset of the C m rise. D—F A similar experiment performed in mutant cell.
Although we found robust secretory responses in both cell types, it appeared that mutant cells lacked the rapid initial phase in the exocytic burst. These longer exocytic delays correspond to the delays that were previously determined for the fusion of vesicles from the SRP 6.
For mutant cells, the exocytic burst generally had a monoexponential time course and the corresponding fusion rate constants matched with the rate constants of the slow component in the control cells. The C m trace from the mutants also was normalized to the C m increase in control cells 1 s after the flash, to illustrate the difference in time course between both groups.
The following parameters were obtained: This reduction could be completely attributed to the absence of fusion of readily releasable vesicles Fig. The rate of sustained release, determined as the slope of a line fitted to the C m traces between 2 and 5 s after a flash, was not affected in the null mutants Fig. Lower time resolution 0. Endocytic membrane retrieval followed an approximately mono-exponential time course with time constants of We conclude that synaptotagmin I is not required for slow, compensatory endocytosis in chromaffin cells.
Under these conditions, amperometric spikes could be measured from both control Fig.
Thomas Voets of KU Leuven, Leuven (ku leuven) with expertise in: Physiology. Read publications, and contact Thomas Voets on ResearchGate, the. View the profiles of professionals named Thomas Voets on LinkedIn. There are 16 professionals named Thomas Voets, who use LinkedIn to exchange. Thomas Voets. KU Leuven Department of Cellular and Molecular Medicine and VIB Center for Brain & Disease Research. Verified email at 321-sports-betting.info