Spermine attenuates carotid body glomus cell oxygen sensing by inhibiting

Abstract

An increase in intracellular Ca2+ is crucial to O2 sensing by the carotid body. Polyamines have been reported to modulate both the extracellular Ca2+-sensing receptor (CaR) and voltage-gated Ca2+ channels in a number of cell types. Using RT-PCR and immunohistochemistry, the predominant voltage-gated Ca2+ channels expressed in the adult rat carotid body were L (CaV1.2) and N (CaV2.2)-type. CaR mRNA could not be amplified from carotid bodies, but the protein was expressed in the nerve endings. Spermine inhibited the hypoxia-evoked catecholamine release from isolated carotid bodies and attenuated the depolarization- and hypoxia-evoked Ca2+ influx into isolated glomus cells. In agreement with data from carotid body, recombinant CaV1.2 was also inhibited by spermine. In contrast, the positive allosteric modulator of CaR, R-568, was without effect on hypoxia-induced catecholamine release from carotid bodies and depolarization-evoked Ca2+ influx into glomus cells. These data show that spermine exerts a negative influence on carotid body O2 sensing by inhibiting L-type Ca2+ channels.