Intracellular pH regulation

The intracellular pH regulation in the brain is as important in physiological and psychopathological conditions. Changes in pH values generally result in altered brain neuronal stimuli. Scientists Vernon A. Ruffin Ahlam Salameh I, Walter F. Boron and Mark D. Parker studied four areas for regulation of pH: 1. pH of the intracellular effect on the functioning of cells, such as the activity of membrane transport channels acid and lye, and neural excitability; 2. intracellular pH homeostasis value which is a balance between the entry and exit of acid; 3. properties and importance of acid-base carriers (primarily SLC4 and SLC9 families) participating in the transfer of acid; 4. the effect of acid-base disturbances in nerve function and the role of acid-base carriers in the defense of stability within the neural pH in psychopathological conditions.

The results reached by the research show that the neural excitability is very sensitive to intracellular and extracellular changes in pH and that acid-base transporters have a very important role; the loss of any of these carriers is associated with serious disorders of neurons. This also applies vice versa – the pH of the disorders is associated with many pathophysiological conditions such as Alzheimer’s and Parkinson’s disease, and has a proven effect on acid-base conveyor severity of signs of a neurological disorder. It is interesting that several clinical neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis include reduction in signs of brain pH. Even diseases that originate outside of the brain can affect the pH of the brain.

Irritable neurons respond to changes in pH value, since the extracellular and intracellular and transmembrane parts of important proteins are sensitive to its changes. Transmembrane proteins act as channels, transporters, receptors or adenosine triphosphate pump, and participate in the management of the membrane potential of neurons at a standstill, affecting the neural response to agonists and antagonists, setting the threshold for triggering action potentials, affecting the duration/amplitude of the action potential, determine the length of the refractory period, and coordinating the activity of neural networks. All these properties make neurons communicate with other neurons and glial cells in the nervous system, for functions such as learning, behavior, conscious thoughts and unconscious homeostatic regulation. They also provide the ability to communicate with cells outside the nervous system, for functions such as motor control and endocrine regulation. It is assumed that the direction in which neurons react depends on the pH response of some channels, transporters and receptors responsible for dictating the overall excitability of neurons. Regulation of cytosolic pH (pH of colloidal fluids within the cell) in most cells, including neurons, is an active process. The processes of filling acid are trying to restore a stable state of pH in neurons after alkaline load. On the other hand, draining acid from neurons is process which aims to raise the pH of the neurons. This process seeks to return to steady state pH in neurons after acid load, which may arise due to the intense activity of neurons.

Respiratory acidosis results from the inability of elimination of CO2 generated by cellular respiration. The consequence is that the partial pressure of CO2 in the blood increases, the pH of the blood is reduced. Respiratory acidosis reduces neural activity and long-term respiratory acidosis leads to disorientation, convulsions, unconsciousness and death. Respiratory alkalosis stems from the excessive elimination of CO2 generated by cellular respiration. The consequence is that the partial pressure of CO2 in the blood falls, the pH value of the blood increases.

Metabolic acidosis is a result of increasing the acid formed in the metabolic processes or inability of removing acid or re-absorption of a base (alkali) in the kidneys. Metabolic acidosis results in decreasing the pH of the blood, and can lead to coma and death. The body reacts to metabolic acidosis mobilizing the bicarbonate buffer system in terms of increasing production of CO2, which can be amplified breathing out. Metabolic alkalosis in turn results in an increase of bicarbonate in the blood, which leads to an increase in the pH of the blood.

The body does not solve the excess acid only by an increased elimination, but also with the help of neutralizing protein, phosphate and carbonate in the bones.