Gain-of-function (GOF) mutations in ion channels are rare events, which lead to increased agonist sensitivity or altered gating properties, and may render the channel constitutively active. Uncovering and following characterization of such mutants contribute substantially to the understanding of the molecular basis of ion channel functioning. Here we give an overview of some GOF mutants in polymodal ion channels specifically involved in transduction of painful stimuli - TRPV1 and TRPA1, which are scrutinized by scientists due to their important role in development of some pathological pain states. Remarkably, a substitution of single amino acid in the S4-S5 region of TRPA1 (N855S) has been recently associat ed with familial episodic pain syndrome. This mutation increases chemical sensitivity of TRPA1, but leaves the voltage sensitivit y unchanged. On the other hand, mutations in the analogous regi on of TRPV1 (R557K and G563S) severely affect all aspects of channel activation and lead to spontaneous activity. Comparison of the effects induced by mutations in homologous positions in different TRP receptors (or more generally in other distan tly related ion channels) may elucidate the gating mechanisms conserved during evolution., S. Boukalova ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Measurements of ryanodine receptor (RyR) activity during dynamic changes of calcium concentration have suggested that RyR has at least four calcium binding sites, and that activation transpires as an increase in the activity within the high open probability H-mode. Binding of several Ca2+ ions within the H-mode should manifest itself in the steady-state RyR activity by the presence of multiple closed times. However, previously only two closed times were detected in the H-mode of RyR activity. Here we recorded steady-state activity of single cardiac RyRs with high temporal resolution and compared it to data simulated under the same conditions using our previously published model of RyR gating. At a 10 kHz resolution, the closed time histograms of both experimental and simulated data had three exponential components. The closed times of simulated data were not significantly different from those obtained experimentally. After filtering at 2 kHz, only two exponential closed time components with time constants not significantly different from those previously published could be detected in both experimental and simulated records. The conformity of the steady-state experimental data to the model derived from the dynamic data provides further support for the idea that RyRs need binding of multiple Ca2+ ions to open., M. Dura, I. Zahradník, A. Zahradníková., and Obsahuje bibliografii
The social consequence of gating have been generally characterized as negative, particularly in regards to raising issues of social injustice such as the privatization of space, estrangement, and segregation. Some authors have found positive social consequences of gating particularly in regard to reducing the scale of segregation and promoting social interdependency as a form of social integration as well as encouraging neighbourhood cohesion and maintaining social capital. The following is a critical review of the positive consequences of gating within the overall trend of commodification of community in new residential developments.
This paper compares the level of neighbourhood cohesion of two single-access neighbourhoods in Calgary, Alberta. The two neighbourhoods had a high sense of neighbourhood cohesion. It is argued that the single access to the neighbourhood has contributed to a high sense of neighbourhood cohesion. One neighbourhood outperformed the other on all three subscales of cohesion due to a stronger sense of seclusion of the neighbourhood. Establishing a sense of identity, a focus, and a clear boundary for a neighbourhood is paramount. At the same time, visionary planning for the future of neighbourhood design with a view to an easy and flexible redevelopment of the open-grid model seems to dominate the mindset of municipal planners operating under the banner of sustainability.