Voltage-Dependent Gating of hERG Potassium Channels

The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv) channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4–S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-à-go-go related gene, hERG), which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure–function relationships underlying activation and deactivation gating in Shaker and hERG channels, with a focus on the roles of the voltage-sensing domain and the S4–S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter-charge interactions. More recent data suggest that key amino acid differences in the hERG voltage-sensing unit and S4–S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor

Citizen Journalism at the Margins

Amidst burgeoning literature on citizen journalism, we still know relatively little about how and why genuinely marginalised groups seek to use this form of reporting to challenge their exclusion. In this article, we aim to address this gap by analysing two UK citizen journalism initiatives emanating from The Big Issue Foundation, a national homeless organisation, and Access Dorset, a regional charity for disabled and elderly people. These case studies are united by the authors’ involvement in both instances, primarily through designing and delivering bespoke citizen journalism education and mentoring. Based on over 40 hours of interviews with participants of the workshops and 36 hours of participant observation, we analyse the challenges participants faced in their journey to become citizen journalists. This included: low self-esteem, physical health and mental wellbeing, the need for accessible and adaptable technology, and overcoming fear associated with assuming a public voice. We also analyse marginalised groups’ attitudes to professional journalism and education, and its role in shaping journalistic identity and self-empowerment. Whilst demonstrably empowering and esteem building,our participants were acutely aware of societal power relations that were seemingly still beyond their ability to influence. Those who are marginalised are, nevertheless, in the best position to use citizen journalism as a conduit for social change, we argue - though challenges remain even at the grassroots level to foster and sustain participatory practices

The Prometheus Leadership Commons: A Meta-Framework for Leadership and Leadership Development

Leadership development suffers a plethora of problems: complexity, competitiveness, pressured stakeholders and unmet needs only start to express the challenges. These issues are suitably summarized by this meta-problem for the subject of leadership: How to navigate the territory? How can a student of leadership, a middle manager, an L&D specialist or a CLO plot a pathway through such a confusing landscape? The Prometheus Project initiated a cross-disciplinary research team to conceptualize a framework that addresses this meta-problem. This paper introduces and discusses the resulting framework, describes our method, and asserts recommendations for expanding the circle of consent for a clear framework for developing the capacities and skills of leadership