A model of O₂ sensing by glomus cells during moderate to severe hypoxia.

Mild hypoxia (>5% O₂) inhibits (step 1) the outward K⁺ current such as TASK via an O₂ sensor. This depolarizes the cell, causing opening of the voltage-gated Ca²⁺ channels (step 2), influx of Ca²⁺ and elevation of [Ca²⁺]_i (step 3). The rise in [Ca²⁺]_i causes transmitter secretion. Moderate and severe hypoxia (<5% O₂) causes stronger inhibition of the outward K⁺ current than that produced by mild hypoxia, producing a greater level of depolarization and a higher [Ca²⁺]_i. Rise of [Ca²⁺]_i beyond ∼200 nm from a basal level of ∼100 nm begins to activate the Na⁺-permeable 20 pS channel (step 4). Na⁺ influx via the 20 pS channel may initiate a feed-forward mechanism (steps 5→3→4→5) to further increase and maintain the levels of depolarization and [Ca²⁺]_i during moderate to severe hypoxia. Depolarization and the associated increase in [Ca²⁺]_i may activate BK (step 6) and limits the feed-forward mechanism and over-depolarization (see text for further explanation). Thus, our model incorporates the role of both K⁺- and Na⁺-permeable channels in the depolarization of glomus cells when hypoxia is moderate to severe.