Modulation of BK channel expression in mouse carotid body

Abstract

The carotid body (CB) is a major arterial chemoreceptor that senses low arterial PO2. Inhibition of large conductance calcium‐activated K+ (BK) channels have been hypothesized to be one of the initial key steps in hypoxic chemotransduction pathways of the glomus cell (GC). Our previous study indicates that the iberiotoxin‐sensitive BK current was more robust in GC of DBA/2J mice (high responder to hypoxia) than that of A/J mice (low responder to hypoxia). Further, glial‐derived neurotrophic factor (GDNF) appears to modulate the expression of BK channels. Since GDNF is induced by oxidative stress, we have hypothesized that oxidative stress and GDNF influences gene expression and function of BK channels, resulting in different phenotype of the GCs between the two strains of mice. We have developed a culturing system for undissociated whole CB. The carotid bifurcations with the CBs were harvested and cultured in defined media with different PO2 levels (21–95% O2) at various durations (4–24 hours). Real‐time PCR analysis revealed that GDNF levels increased in all cultured conditions tested in both strains, but the levels returned toward the control after 24 hours of culture. BKβ4 expression was similar to GDNF expression, while BKα1 and BKβ2 expression did not show consistent changes. Exposure of the DBA/2J's CB to anti‐GDNF for 12 hours decreased BKα1, β2, β4 mRNA expressions. These results are complimentary to our previous study showing that supplementation of GDNF in the A/J's CB increased functional expression of BK channels. The results further suggest that BKβ4 subunit expression may be influenced by environmental O2.Supported by HL72293 & HL 081345