The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape

Abstract

<jats:title>Abstract</jats:title><jats:p>Several ion channels can be randomly and spontaneously in an open state, allowing the exchange of ion fluxes between extracellular and intracellular environments. We propose that the random changes in the state of ion channels could be also due to proteins exploring their energy landscapes. Indeed, proteins can modify their steric conformation under the effects of the physicochemical parameters of the environments with which they are in contact, namely, the extracellular, intramembrane and intracellular environments. In particular, it is proposed that the random walk of proteins in their energy landscape is towards attractors that can favor the open or close condition of the ion channels and/or intrinsic activity of G-protein-coupled receptors. The main aspect of the present proposal is that some relevant physicochemical parameters of the environments (e.g. molecular composition, temperature, electrical fields) with which some signaling-involved plasma membrane proteins are in contact alter their conformations. In turn, these changes can modify their information handling via a modulatory action on their random walk towards suitable attractors of their energy landscape. Thus, spontaneous and/or signal-triggered electrical activities of neurons occur that can have emergent properties capable of influencing the integrative actions of brain networks. Against this background, Cook’s hypothesis on ‘cell sentience’ is developed by proposing that physicochemical parameters of the environments with which the plasma-membrane proteins of complex cellular networks are in contact fulfill a fundamental role in their spontaneous and/or signal-triggered activity. Furthermore, it is proposed that a specialized organelle, the primary cilium, which is present in most cells (also neurons and astrocytes), could be of peculiar importance to pick up chemical signals such as ions and transmitters and to detect physical signals such as pressure waves, thermal gradients, and local field potentials.</jats:p>

Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review)

“…It describes a system able to sense the external world in order to produce a response to perturbations either by self-correction of its disturbed organization (homeostasis), or by reorganizing itself into a different self-perpetuating network of interactions (adaptability). There are, of course, various levels of cognition (corresponding to different levels of life's complexity) from very simple mechanisms of cell sentience (36) up-to complex functions performed by nervous systems.…”

“…2). This action may contribute in clearing debris from the ventricle walls, and may enhance mixing, which may be particularly relevant for neuroendocrine communication (57) or even for signal detection (36). Thus, while some short-distance volume transmission (VT)-signalling can rely upon this action of the ependymal cilia close to the walls of lateral ventricles, long-distance VT-signalling could be mainly driven by wall motion and CP pulsation, hence by CSF dynamics in the centre regions of the ventricles, according to the tide hypothesis (58).…”