AMPA Receptor-Dependent Glutamatergic Signaling is Present in the Carotid Chemoreceptor

•Multiple AMPA receptors, kainate receptors as well as glutamate transporters were expressed in rat carotid body.•Treatment of rat carotid body-derived primary cells with AMPA activated ERK1/2 in a time-dependent manner.•Exposing SD rats to CIH for 8 h/day for 3 weeks significantly enhanced the expression of GluA1 mRNA as well as its protein.•AMPA receptors as well as its associated PSD-MAGUK molecules were also present in human carotid body. Exposure to both sustained and intermittent hypoxia for as little as a day produces sustained augmentation of carotid chemoreceptor sensitivity; however, the molecular basis for this chemoreflex plasticity remains uncertain. We previously reported that NMDA receptor-dependent glutamatergic signaling in rat carotid body played a role in altered hypoxic sensitivity after exposure to cyclic intermittent hypoxia (CIH). Here we found that mRNAs of multiple AMPA and Kainate glutamate receptors were expressed in rat carotid body. The AMPA receptor subunit GluR1 showed intense immunoreactivity in the carotid body, co-localizing with tyrosine hydroxylase in type I cells. Treatment of rat carotid body-derived primary cells with AMPA activated ERK1/2 in a time-dependent manner. Exposing Sprague–Dawley rats to CIH for 8 h/day for 3 weeks significantly enhanced the expression level of GluA1 mRNA as well as GluR1 protein in the carotid body. In addition, our results showed that multiple of vesicular glutamate transporters (VGLUTs) and excitatory amino acid transporters (EAATs) were expressed in the rat carotid body, indicating that glutamate might be as a neurotransmitter stored, released and uptake in the carotid body. Finally, we found that mRNAs of GluA1, GluA2 and GluA3 as well as PSD-95-like membrane-associated granulate kinase family members, PSD-95, PSD-93, and SAP97, were expressed in human carotid body. Our data suggest AMPA receptor-dependent glutamatergic signaling is present in the carotid body and might be involved in the carotid chemoreceptor response to hypoxia.