Functional Interactions between KCNE1 C-Terminus and the KCNQ1 Channel

The KCNE1 gene product (minK protein) associates with the cardiac KvLQT1 potassium channel (encoded by KCNQ1) to create the cardiac slowly activating delayed rectifier, IKs. Mutations throughout both genes are linked to the hereditary cardiac arrhythmias in the Long QT Syndrome (LQTS). KCNE1 exerts its specific regulation of KCNQ1 activation via interactions between membrane-spanning segments of the two proteins. Less detailed attention has been focused on the role of the KCNE1 C-terminus in regulating channel behavior. We analyzed the effects of an LQT5 point mutation (D76N) and the truncation of the entire C-terminus (Δ70) on channel regulation, assembly and interaction. Both mutations significantly shifted voltage dependence of activation in the depolarizing direction and decreased IKs current density. They also accelerated rates of channel deactivation but notably, did not affect activation kinetics. Truncation of the C-terminus reduced the apparent affinity of KCNE1 for KCNQ1, resulting in impaired channel formation and presentation of KCNQ1/KCNE1 complexes to the surface. Complete saturation of KCNQ1 channels with KCNE1-Δ70 could be achieved by relative over-expression of the KCNE subunit. Rate-dependent facilitation of K+ conductance, a key property of IKs that enables action potential shortening at higher heart rates, was defective for both KCNE1 C-terminal mutations, and may contribute to the clinical phenotype of arrhythmias triggered by heart rate elevations during exercise in LQTS mutations. These results support several roles for KCNE1 C-terminus interaction with KCNQ1: regulation of channel assembly, open-state destabilization, and kinetics of channel deactivation

Stakeholder perceptions of the importance and effects of sustainability education

This chapter discusses the role that universities are expected to play in addressing sustainability-related issues, noting a lack of agreement on definitions for key terms and on the most effective way to include relevant content within the curriculum. These debates need to be seen within the context of calls to ensure that graduates are ‘work ready’. The way that sustainability issues are addressed in curriculum, and the impact on subsequent attitudes, beliefs and behaviours has been the subject of considerable debate in both academic and industry outlets. We discuss a multi-phase study by an Australian regional university that has made significant investment in integrating sustainability into all subjects within undergraduate business degrees. This investment was informed both by the academic debate on sustainability issues and by discussions with potential employers. We review the curriculum changes and examine key stakeholders’ views regarding the importance of both sustainability specifically and overall work readiness of graduates. The chapter concludes with a discussion of strategies for ongoing fine-tuning of business curricula and for ongoing engagement with current and prospective employers regarding sustainability-related issues within the wider context of equipping graduates with the skills and abilities valued by prospective employers in a rapidly changing workplace