Kv7 Channels Can Function without Constitutive Calmodulin Tethering

M-channels are voltage-gated potassium channels composed of Kv7.2-7.5 subunits that serve as important regulators of neuronal excitability. Calmodulin binding is required for Kv7 channel function and mutations in Kv7.2 that disrupt calmodulin binding cause Benign Familial Neonatal Convulsions (BFNC), a dominantly inherited human epilepsy. On the basis that Kv7.2 mutants deficient in calmodulin binding are not functional, calmodulin has been defined as an auxiliary subunit of Kv7 channels. However, we have identified a presumably phosphomimetic mutation S511D that permits calmodulin-independent function. Thus, our data reveal that constitutive tethering of calmodulin is not required for Kv7 channel function

Encouraging and supporting children's voices

Children are considered not to be full members of society and that their participation should be limited. Further, that this limitation is imposed by adults. In order to counter these views it is key to afford space for children’s voices and that these are facilitated in some way. Philosophy with Children, in all its variety of approaches and practices, lays claim to being a tool that allows children to develop the skills necessary for citizenship such as participation and airing their views. The chapter focuses on the role of Community of Philosophical Inquiry (CoPI), a specific method of practical philosophy with children, to empower children and give them a voice. CoPI has a series of distinctive features that make it especially apt in meeting this goal. Children are able articulate their views on a particular topic and this is supported by the structure of the dialogue itself. In addition, though, their statements must build on previous statements by demonstrating dis/agreement and the participants must provide reasons to justify that dis/agreement. The method also emphasises the primacy of the children’s thinking and the facilitator works to juxtapose speakers in order to drive the dialogue further philosophically. In this chapter, these features of CoPI are illustrated by examples from dialogues on the Good Life, stimulated by the question "What kind of society would you like to live in?" CoPI is shown to give children voice with a view to promoting their participation in society while also eschewing the imbalance in the adult/child power relationship. Here, we see what is important to children in the lives they want to live, for themselves and for those around them. What is of particular interest is the manner in which the children appear to collude with the adult/child power divide in how they talk about the kind of society in which they’d like to live

Selective Interaction of Syntaxin 1A with KCNQ2: Possible Implications for Specific Modulation of Presynaptic Activity

KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability. Notably, they differ from homomeric KCNQ2 channels in their distribution pattern within neurons, with unique expression of KCNQ2 in axons and nerve terminals. Here, combined reciprocal coimmunoprecipitation and two-electrode voltage clamp analyses in Xenopus oocytes revealed a strong association of syntaxin 1A, a major component of the exocytotic SNARE complex, with KCNQ2 homomeric channels resulting in a ∼2-fold reduction in macroscopic conductance and ∼2-fold slower activation kinetics. Remarkably, the interaction of KCNQ2/Q3 heteromeric channels with syntaxin 1A was significantly weaker and KCNQ3 homomeric channels were practically resistant to syntaxin 1A. Analysis of different KCNQ2 and KCNQ3 chimeras and deletion mutants combined with in-vitro binding analysis pinpointed a crucial C-terminal syntaxin 1A-association domain in KCNQ2. Pull-down and coimmunoprecipitation analyses in hippocampal and cortical synaptosomes demonstrated a physical interaction of brain KCNQ2 with syntaxin 1A, and confocal immunofluorescence microscopy showed high colocalization of KCNQ2 and syntaxin 1A at presynaptic varicosities. The selective interaction of syntaxin 1A with KCNQ2, combined with a numerical simulation of syntaxin 1A's impact in a firing-neuron model, suggest that syntaxin 1A's interaction is targeted at regulating KCNQ2 channels to fine-tune presynaptic transmitter release, without interfering with the function of KCNQ2/3 channels in neuronal firing frequency adaptation