Carbon monoxide and carotid body chemoreception.

Abstract

It is being increasingly recognized that endogenously generated carbon monoxide (CO) functions as a chemical messenger in the nervous system. CO is released during the breakdown of heme to biliverdin by the enzyme heme oxygenase (HO). Two isoforms of HO have been identified: HO-1 is an inducible form and is found predominantly in spleen and liver; HO-2 is constitutive and is widely distributed in brain and nervous tissues (Verma et al, 1993). We have recently reported that HO-2 is present in the carotid bodies where it is found primarily in the glomus cells (Prabhakar et al, 1995). More importantly, we showed that zinc protoporphyrin-9 (ZnPP-9), an inhibitor of HO, increased chemoreceptor activity, suggesting that endogenous CO is inhibitory to carotid body (CB) activity. In the present study we assessed cellular mechanisms by which endogenous CO modulates CB activity. It is generally accepted that Ca2+-dependent neurotransmitter release from glomus cells plays an important role in transduction of a hypoxic stimulus by the CB. Therefore, we tested the idea that endogenous CO exerts its effects on carotid body sensory activity in part by regulating cytosolic calcium ([Ca2+]I) in glomus cells. To test this possibility we monitored [Ca2+]I and ion channel activities in glomus cells in response to ZnPP-9, an inhibitor of CO synthesis.