Expression of BK (large conductance calcium‐activated K) channel subunits and oxygen sensitivity of glomus cells in mice

Abstract

The carotid body (CB) is a primary oxygen sensor, and oxygen sensitivity of K channels in glomus cells (GCs) may be responsible for hypoxic sensing. Hypoxic sensitivity of the CB appears to be genetically determined. In mice, the DBA/2J strain responds vigorously to hypoxia, but the A/J strain responds weakly. We have hypothesized that differential expression of oxygen‐sensitive K channels, especially BK channels, causes different hypoxic sensitivity of the two strains of mice. Gene expression of BK channel subunits in the CB was examined with RT‐PCR analysis. Actin was used as a reference gene after validating its use among total five housekeeping genes. We found that α and β2 subunits were more expressed in DBA/2J mice than A/J mice. No differences were found in the expression of the β4 subunit between the two strains. The role of BK channels in hypoxic sensitivity was examined in patch clamp experiments using undissociated CBs. Voltage‐dependent outward K current in GCs was inhibited by 4‐aminopyridine in both mice. Iberiotoxin significantly inhibited K current in DBA/2J mice, but not in A/J mice. With decreasing PO2 to ~70 mmHg, K current declined in GCs of DBA/2J, but not A/J mice. With the presence of iberiotoxin, mild hypoxia did not inhibit K current in either strain of mice. In accordance with these results, mild hypoxia increased intracellular Ca2+ in GCs of DBA/2J mice, but not in A/J mice. The data suggest that BKαβ2 channels are extremely sensitive to PO2 changes, and thus, GCs in DBA/2J mice are sensitive to mild hypoxia. It is possible that BKβ4 subunits interferes functional expression of BK channels. In A/J mice, in addition to lower expression of pore‐forming α subunits, higher expression of β4 subunits relative to other subunits may cause lower hypoxic sensitivity of the GC. Support: HL81345, AHA09GRNT2080158