Lactate Hypothesis

Question 1

The most recently developed hypothesis by Chang 2015

Answer 1

Potential role of lactate accumulation in acute O2 sensing by CB

Question 2

Chang et al identified an olfactory receptor gene

Answer 2

Olfr78 in type I glomus cells

Question 3

Interestingly, Olfr78 KO mice

Answer 3

Reduced responses to hypoxia with loss of acute HVR

Question 4

Lactate-Olfr78 hypothesis put forth involves

Answer 4

inhibition of electron transport in glomus cell mitochondria during hypoxia which leads to formation of lactate from glucose

Question 5

Lactate accumulation proposed to

Answer 5

activate Gprotein receptor Olfr78 to depolarise glomus cell and increase CB activity

Question 6

Several arguments to oppose theory

Answer 6

> questions regarding sensitivity of Olfr78 to lactate
reported to only be sensitive to lactate outside a certain phys range
failure to replicate abolished HVR in other KO mice studies

Question 7

In addition, an alternative lactate theory proposed by Torres-Torrelo (2021)

Answer 7

involves lactate-induced increase in cytosolic NADH/NAD+ ratio and mitochondrial ROS production to modulate activity of membrane ion channels - to disregard involvement of Olfr78