Molecular identification and functional role of voltage‐gated sodium channels in rat carotid body chemoreceptor cells. Regulation of expression by chronic hypoxia in vivo
Publication
, Journal Article
Caceres, AI; Obeso, A; Gonzalez, C; Rocher, A
Published in: Journal of Neurochemistry
We have assessed the expression, molecular identification and functional role of Na channels (Na) in carotid bodies (CB) obtained from normoxic and chronically hypoxic adult rats. Veratridine evoked release of catecholamines (CA) from an preparation of intact CBs obtained from normoxic animals, the response being Ca and Na‐dependent and sensitive to tetrodotoxin (TTX). TTX inhibited by 25–50% the CA release response evoked by graded hypoxia. Immunoblot assays demonstrated the presence of Naα‐subunit ( 220 kDa) in crude homogenates from rat CBs, being evident an up‐regulation (60%) of this protein in the CBs obtained from chronically hypoxic rats (10% O; 7 days). This up‐regulation was accompanied by an enhanced TTX‐sensitive release response to veratridine, and by an enhanced ventilatory response to acute hypoxic stimuli. RT‐PCR studies demonstrated the expression of mRNA for Na1.1, Na1.2, Na1.3, Na1.6 and Na1.7 isoforms. At least three isoforms, Na1.1, Na1.3 and Na1.6 co‐localized with tyrosine hydroxylase in all chemoreceptor cells. RT‐PCR and immunocytochemistry indicated that Na1.1 isoform was up‐regulated by chronic hypoxia in chemoreceptor cells. We conclude that Na up‐regulation represents an adaptive mechanism to increase chemoreceptor sensitivity during acclimatization to sustained hypoxia as evidenced by enhanced ventilatory responses to acute hypoxic tests.
