Glial cell-derived neurotrophic factor (GDNF) induced expression of calcium-activated large conductance K (BK) channels in mouse glomus cells (GC).

Autor: Koichi Fujii, Balbir, Alex, Otsubo, Toshiki, Okumura, Mariko, Shirahata, Machiko
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Zdroj: FASEB Journal; Apr2007, Vol. 21 Issue 6, pA924-A925, 2p
Abstrakt: DBA/2J mice, but not A/J mice, respond robustly to hypoxia, suggesting the function of the carotid body (CB) differs between these mice. Previous studies show that BK channels play a role in hypoxic chemotransduction in the CB. We have hypothesized that: (1) BK channel expression differs between the two strains of mice; (2) GDNF contributes to the different expression of BK channels in these mouse CBs. First, we examined the gene expression for GDNF and for BK channel subunits (α, β2, β4) in the CB harvested from 1-2 week-old mice with RT-PCR analysis. GDNF, BKα and BKβ are more expressed in the CB of the DBA/2J mouse than in that of the A/J mouse. Second, we have investigated the effects of GDNF or anti-GDNF on BK channel expression. Carotid bifurcations including the CB were cultured for 2 days in chemically defined media. The supplementation of GDNF (100 nM) in A/J mice upregulated BK channel α and β2 subunits expression. On the other hand, the supplementation of anti-GDNF antibody (1 µg/ml) in DBA/2J mice downregulated BK channel α and β2 subunits expression. Third, patch clamp experiments showed that without GDNF supplementation iberiotoxin-sensitive BK current was observed in GCs of DBA/2J mice, but not in GCs of A/J mice. When supplemented withGDNF, GCs of A/J mice expressed iberiotoxin-sensitive BK current. The results indicate that GDNF contributes to the functional expression of BK channels in mouse GCs. [ABSTRACT FROM AUTHOR]
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