How do animals know when to take a breath? Whether the animal is awake or asleep, and during exercise or at rest, the respiratory system carefully regulates breathing patterns to maintain oxygen uptake without the need for conscious thought. Scientists have long known that specialized cells continually monitor the pH and levels of oxygen and carbon dioxide in the blood and these cells send neural impulses to stimulate breathing if these parameters move away from normal values. More recently, experiments in rats and mice have found that the common organic compound lactate, produced by animals when not enough oxygen is available, also stimulates breathing. However, it is unknown whether this mechanism of respiratory control is unique to mammals or a trait shared by all vertebrates.
A new study, led by Mikkel Thomsen at Aarhus University, Denmark, tested the hypothesis that respiration in fishes is controlled by the amount of lactate in the blood just like it is in mammals. The authors performed careful surgeries on rainbow trout (Oncorhynchus mykiss), inserting a tiny tube into the bloodstream so that they could inject lactate to directly manipulate levels in the blood. They also attached an electrical probe to the bony plate that covers the gills, allowing them to measure the amplitude and frequency of the fish's breathing movements.
Just as the authors hypothesized, addition of lactate to the bloodstream stimulated trout to take larger, deeper breaths, but the frequency of breathing did not change. To see whether the fish could respond to the precise amount of lactate in the blood, the authors added different quantities through the plastic tubing and found that the more lactate they added, the deeper the breaths of the fish. Thus, lactate seems capable of transmitting detailed information about the oxygen requirements of the fish.
Next, the authors asked how trout sense changes in circulating lactate levels. Specialized cells in the gills of other fishes are known to sense oxygen levels in the blood and signal for increased breathing, so perhaps these could also sense lactate. First, Thomsen and his colleagues painstakingly removed the gills that contain most of these sensory cells and, as predicted, the breathing of these fish hardly increased when they were given lactate injections. Next, the authors injected intact fish with a variety of drugs that are known to target the gill sensory cells. In the presence of these drugs, lactate injections did not stimulate breathing, strongly indicating that the lactate signal is received by sensory cells in the trout's gills. Finally, the researchers wanted to know whether the lactate sensors in trout shared an evolutionary history with those already discovered in mammals, or whether the fish used a different mechanism to keep tabs on blood lactate. Searching through the genetic code of the trout, the authors found a gene that looked remarkably like the one that codes for the lactate sensor in mammals. Thus, it seems that all vertebrates, whether furry or fishy, may share a signalling system that uses lactate to stimulate breathing.
Of course, many more animals should be investigated before we can conclude that lactate is a universal respiratory stimulant, but the benefits of this simple signalling system are clear. When oxygen is limited, animals take an energetic loan in the form of lactate. Then, to pay off this ‘oxygen debt’, lactate acts as its very own debt collector, stimulating deeper breathing and hence increased oxygen uptake. No middlemen required.