The authors of this fabulously informative and also historically fascinating article were among the earliest researchers to grasp the significance of ATP in the determination and guidance of how life functions on our planet… " As they state here, " One of the first and most enduring facts most students learn in biology class is that all living cells use a small molecule called adenosine triphosphate (ATP) as fuel. That universal energy currency drives the biological reactions that allow cells to function and life to flourish—making ATP a crucial player in the biological world "
However this first role of as the everpresent fuel for cellular functioning, evolutionarily conserved throughout species was merely the beginning of the awareness of its importance. We suspect that, partly due to our science's never escaped tendency to view events, in life as well as elsewhere in nature as mechanistically determined, the ATP molecules and its metabolites were typecast as fuel for the functioning of cells.
Within the brain where the processes of cognition and the neurons involved demand high levels of energy, ATP was thus respected as a key fuel of brain activity, but it was not considered that since the brain does not truly function like a mechanical device, the same molecule that serves intracellularly as fuel would also be released extracellularly by those neurons (and more recently by the astrocytic cells which support them) as a messenger and signal to other cells in the brain.
What we today know from other recent research on astrocytes find can truly appreciate after seeing the history of the increase in respect for ATP and the various purinergic receptors through which it acts so crucially within the brain, is that ATP is unsurprisingly the key to the communication and synergy because the fundamental life of the astrocyte scaffolding of interconnected glial cells and the many neuronal assemblies and networks of the brain.
ATP is how they talk to each other and manage to support each other and, as manifest in most of the phenomena of so-called " consciousness' to synergize and synchronize with each other. And why should not the very elixir of life, in a manner of speaking, the energy source of ATP, not be chosen by evolution and intelligent design of whatever kind we might prefer to speak of as the most effective messenger to other cells of just how things are going, for better or worse as the organized tissues of the body continue to function as best as they can?
We find that we cannot possibly understand anything in neuroscience nowadays with an awareness and further exploration of how indeed it is that there are receptors on both neurons and glial cells that are triggered by extracellular ATP that is released and due to other cells and then, among a multitude of other effects, manages to regulate the crucial Ca++ events in the cell, sometimes opening up various channels to accept incoming Calcium ions and sometimes triggered other receptors to stimulate release of Calcium from internal stores. This Calcium conversation is the language by means of which the ATP molecules contrive to allow the cells and, importantly, the assemblies and networks of cells in the brain to talk to each other…and to work together.
What we find out is , again, not so surprisingly in retrospect. is that if the living organism is not considered to be either a mechanical device or some sort of " obscure " information exchanging device , then life has managed to give 'meaning " to what seem like basic mechanistic events. This allows conversation to occur on a level far beyond that of brute information (which is essentially a fairy tale to rationalize observations retrospectively but without providing any clue as to the nature and meaning of any constituent processes that might lead to the observation of those who chant the " information " mantra. "Information" much like 'Emergence" is another sugar coated story for scientists and philosophers to fall back upon ---when they can't have anything useful to say…in order to give the appearance of some sort of explanatory narrative which doesn't truly explain anything.
If the organism is to function most effectively , then the ATP would be a signal devised by life as it organizes, that is pregnant and overflowing with meaning. It would indicate the effectiveness of the metabolic process in simply producing ATP, then the demands and utilization of the energy containing within the ATP, and then the possible adverse effect to cells which might via damage of one kind or another release the ATP, or which through life circumstances would require a heightened level of coordination among the constituent other cells performing in their network and relates networks of astrocytes, and then, as well, to determine when and how the ongoing advent of progenitor cells would be triggered if and when needed and when the milieu is appropriate.
Thus the molecules of ATP speak volumes about the global picture in which each cell is functioning via the sharing of that niche with other " like-kinded " or " like-minded " cells with common function. Today, we can go even further and explore the key role that ATP messaging and the related aspects of that messaging, such as the entire new world of microRNA's which intertwine so intimately with ATP have in the disarray that occurs in the systems of various tissues when we note cancer.
The manner in which energy is produced, dispersed, and consumed ..or believed to be via the nature of the communications pertaining to it…. is not only critical to all the turf wars in our world of politics today, but is crucial to the stability of our inner world of our bodies as much as it is to the stability of our outer geopolitical status.
As a final note, we can see again from an intimate insider's perspective how arduous and prolonged the struggle to bring to light various key insights can be. The quest by these authors to overcome the reluctance to view ATP as a messenger while being blinded because it is importance as energy is also a revelation, although it should not be by now, after many such instances of what is practically " self-evident " not being evident at all to the more limited perspectives and self sabotaging conceptual models of the research community.
PART DEUX:
Inseparable Tandem: Evolution Chooses ATP and Ca++ to Control Life, Death and Cellular Signalling
For those who either do not believe our enthusiastic assertions about the incredible importance of the ATP/Calcium connection or who wish to follow up the consequences of this general picture which we painted here in regard to the publication of a few years by the pioneers in ATP research, here is a very recent publication that begins to spell out just how important the ATP/Calcium connection is for all life and especially for our Brains:
http://rstb.royalsocietypublishing.org/content/371/1700/20150419This is an entire volume of research on this theme: They introduce it as follows:
"From the very dawn of biological evolution, ATP was selected as a multipur- pose energy-storing molecule. Metabolism of ATP required intracellular free Ca++ to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca++as a universal signalling molecule.
The early-eukaryote life forms also evolved functional compartmentalization and vesicle trafficking, which used Ca++ as a universal signalling ion; simi- larly, Ca++is needed for regulation of ciliary and flagellar beat, amoeboid movement, intracellular transport, as well as of numerous metabolic pro- cesses.
Thus, during evolution, exploitation of atmospheric oxygen and increasingly efficient ATP production via oxidative phosphorylation by bac- terial endosymbionts were a first step for the emergence of complex eukaryotic cells.
Simultaneously, Ca++ started to be exploited for short- range signalling, despite restrictions by the preset phosphate-based energy metabolism, when both phosphates and Ca++interfere with each other because of the low solubility of calcium phosphates.
The need to keep cytosolic Ca++ low forced cells to restrict Ca++signals in space and time and to develop energetically favourable Ca++ signalling and Ca++ microdomains.
These steps in tandem dominated further evolution.
The ATP molecule (often released by Ca++-regulated exocytosis) rapidly grew to be the universal chemical messenger for intercellular communication; ATP effects are mediated by an extended family of purinoceptors often linked to Ca++ sig- nalling. Similar to atmospheric oxygen, Ca++ must have been reverted from a deleterious agent to a most useful (intra- and extracellular) signalling molecule.
Invention of intracellular trafficking further increased the role for Ca++ homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca++and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story.
