In this foremost study, Sun et al (2019) provide evidence that, in Angelman syndrome models, calcium- and voltage-dependent big potassium BK channel antagonists normalize neuronal excitability. It is known that changes in the BK pore shape and surface hydrophobicity in the Ca2+-free state allow the channel to readily undergo hydrophobic dewetting transitions, giving rise to a large free energy barrier for K+ permeation (Jia et al., 2018). Dewetting transition takes place inside the hydrophobic pores of ion channels. This transient phenomenon causes a metastable state that forbids water molecules to cross microscopic receptor cavities. This leads to a decreased conductance, a closure of the pore and, subsequently, severe impairment of cellular performance. It has been suggested that artificially-provoked dewetting transition in ion channel hydrophobic pores might stand for a molecular candidate to erase detrimental organisms (Tozzi, 2019). A novel type of high-affinity monoclonal antibody has been recently described, that: a) targets specific trans-membrane receptor structures; b) is equipped with lipophilic and/or hydrophobic fragments that prevent physiological water flow inside ion channels. Therefore, artificial dewetting transition is achieved inside receptor cavities, that causes discontinuity within transmembrane ionic flows, channel blockage, and subsequent damage of the target cells. In the case of Angelman syndrome models, these dewetting monoclonal antibodies that target BK channels might prevent water from entering pores, thus leading to normalized neuronal excitability.
Brain activity takes place in three spatial-plus time dimensions. This rather obvious claim has been recently questioned by papers (including this foremost one by Stringer et al.) that, taking into account the big data outburst, are starting to unveil a more intricate state of affairs (see: https://www.sciencedirect.com/science/article/pii/S1571064519300089 ).
Various brain activities and their correlated mental functions can be assessed in terms of trajectories embedded in phase spaces of dimensions higher than the canonical ones. It has been proposed that further dimensions may not just represent a convenient methodological tool that allows a better mathematical treatment of otherwise elusive cortical activities, but may also reflect genuine functional or anatomical relationships among real nervous functions.
In particular, the observed multidimensional representations of behavior reported by Stringer et al. subtend a spontaneous nervous activity that has been recently described as taking place inside a four-dimensional donut-like manifold.
JOURNAL OF NEUROSCIENCE