Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review.

This article addresses the disparity in the transduction pathways for hypoxic and hypercapnic stimuli in carotid body glomus cells. We investigated and reviewed the experimental evidence showing that the response to hypoxia, but not to hypercapnia, is mediated by 1,4,5-inositol triphosphate receptors (IPR/s) regulating the intracellular calcium content [Ca] in glomus cells. The rationale was based on the past observations that inhibition of oxidative phosphorylation leads to the explicit inhibition of the hypoxic chemoreflex.

Effects of iron-chelators on ion-channels and HIF-1alpha in the carotid body.

Acute hypoxia instantaneously increases the chemosensory discharge from the carotid body, increasing ventilation mostly by inhibiting the oxygen sensitive ion channels and exciting the mitochondrial functions in the glomus cells. On the other hand, Fe2+-chelation mimics hypoxia by inhibiting the prolyl hydroxylases and the degradation of HIF-1alpha in non-excitable cells. Whether Fe2+-chelation can inhibit the ion channels giving rise to the sensory responses in excitable cells was the question.

Activation of HIF-1alpha mRNA by hypoxia and iron chelator in isolated rat carotid body.

The hypoxia inducible factor-1alpha (HIF-1alpha) protein level is increased by hypoxia and iron chelator (ciclopirox olamine) in isolated rat carotid body (CB) and glomus cells. Reverse transcription and polymerase chain reaction (RT-PCR) are performed to test whether this increase is caused, at least in part, by increased HIF-1alpha gene transcription. HIF-1alpha mRNA levels dose-dependently increased and decreased in the rat CBs incubated for 1 h in a medium saturated with O(2) levels that were varied around nominally normoxic level of 21% in the 0-95% range.

Extra- and intracellular free iron and the carotid body responses.

The hypothesis that chelation of free iron, by decreasing reactive oxygen species (ROS), might mimic hypoxia and stimulate the carotid body was tested. We used the iron chelators, desferrioxamine (DFO, 200-400 microM) initially, and later ciclopirox olamine (CPX, 2.5-5.

CO-induced K(+) currents in rat glomus cells are insensitive to light unlike carotid body neural discharge and Vo(O(2)).

The hypothesis that the light sensitive properties of CO-induced chemosensory nerve (CSN) discharge and oxygen consumption of the carotid body (CB) were shared by the pre-synaptic glomus cells was tested. The light effect on K(+) currents were measured before and during perfusion of the isolated rat glomus cells with high P(CO) of 550 Torr during nomoxia (P(O(2)approximately equal 100 Torr) at extra-cellular pH 7.0 and intracellular pH 6.