The human body has a mechanism to maintain a certain balanced pH (potential of Hydrogen), or the degree of acidity or alkalinity in the body. Generally, this is found to be around 7.35 (on a scale of 0-14), and it varies throughout the day, depending on one’s diet and activities. The pH levels in tissues are far more sensitive. A slight decrease in the pH, that is a slight increase in acidity in tissues, is called Tissue Acidosis; the degree of acidosis is relies on the circulating glucose concentrations, and conditions like Hyperglycemia or increased blood sugar level causes higher degree of acidosis.
It is well known that tissue acidosis, along with high lactate concentrations, are associated with cerebral ischemia--an unfamiliar word in the household context. Ischemia is the condition where there is a shortage of blood supply to a certain parts of the body. There are various types of ischemia, and the one concerning the braincerebrum is ‘Cerebral ischemia’.
Along with a number of other agents, lactates and protons have been found to activate the potassium channel TREK1 and its increased activity has shown to hinder ischemic cell damage. hTREK1 is an intracellular ionic channel through which potassium ions travel in and out of the cell. In a new study by the Molecular Biophysics Unit, Indian Institute of Science, Bangalore, it was observed that a certain concentration of lactate(30 mM) at pH 7.0 and 6.5, levels which are generally seen during ischemia, can cause booming increase in the effect of hTREK1 activity. While the same concentration of lactate at pH 6.0 and 5.5, observed during hyperglycemic ischemia, reduces the activity of hTREK1 significantly. The effects of 30 mM lactate concentrations ̶ also known as ischemic concentration ̶ is very specific and when experiments were conducted with 3 mM lactate and 30 mM pyruvate at pH 7.0 and 5.5, it failed to show similar results as that of lactate (30 mM).
Since hTREK1 is a gene which can be experimented upon, it was further subjected to deletion and mutation. From this, it was inferred that lactate changes the pH modulation of hTREK1 by behaving differently with Histidine, which is an amino acid residue. This is the first time that such varying effect of pH-dependent lactate on the normal functioning of an ion channel has been reported. This plays an important role in recognizing and addressing different stages of ischemia.