Lactate and Short‐Chain Fatty Acids on Ca2+ Oscillations in Rat Carotid Body Type 1 Cells

Abstract

Carotid body (CB) Type 1 (glomus) cells express Olfr78, a Gs‐coupled receptor that binds lactate and short chain fatty acids. Lactate is produced in all cells under anaerobic conditions, and short chain fatty acids are produced by bacterial fermentation in the colon. Lactate‐Olfr78 signaling has been proposed to be involved in hypoxia‐induced excitation of CB, but this idea is currently controversial. Ca oscillations are low‐level Ca signals in glomus cells. Here we compared the effects of lactate/short chain fatty acids and hypoxia on Ca oscillations in isolated glomus cell. Lactate ≈ acetate > propionate (1–20 mM) produced a concentration‐dependent increase in the frequency of Ca oscillations with no overall effects on the background TASK K current and resting cell membrane potential. Verapamil abolished Ca oscillations with or without lactate. Forskolin (2–10 μM) produced no significant effect on Ca oscillations, suggesting that adenylyl cyclase/cAMP may not be involved in lactate‐induced changes in Ca signaling. H‐89 (1 μM) did not block lactate‐induced increase in Ca oscillations, questioning the role of PKA. Comparison of lactate and hypoxia effects on Ca oscillations indicated that 5–10 mM lactate and 2–5%O2 (mild‐moderate) hypoxia produce similar effects on Ca oscillations. Thus, an increase of blood lactate to 5–10 mM may be necessary to mimic the effect of mild‐moderate hypoxia on Ca signaling in CB glomus cells.