Lactate sensing mechanisms in arterial chemoreceptor cells.

Classically considered a by-product of anaerobic metabolism, lactate is now viewed as a fundamental fuel for oxidative phosphorylation in mitochondria, and preferred over glucose by many tissues. Lactate is also a signaling molecule of increasing medical relevance. Lactate levels in the blood can increase in both normal and pathophysiological conditions (e.

Acute O Sensing: Role of Coenzyme QH/Q Ratio and Mitochondrial ROS Compartmentalization.

Acute O sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O-sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O-sensitive cells have unique metabolic characteristics that favor the hypoxic generation of mitochondrial complex I (MCI) signaling molecules, NADH and reactive oxygen species (ROS), which modulate membrane ion channels.

HIF-2α is essential for carotid body development and function.

Mammalian adaptation to oxygen flux occurs at many levels, from shifts in cellular metabolism to physiological adaptations facilitated by the sympathetic nervous system and carotid body (CB). Interactions between differing forms of adaptive response to hypoxia, including transcriptional responses orchestrated by the Hypoxia Inducible transcription Factors (HIFs), are complex and clearly synergistic. We show here that there is an absolute developmental requirement for HIF-2α, one of the HIF isoforms, for growth and survival of oxygen sensitive glomus cells of the carotid body.

Monitoring Functional Responses to Hypoxia in Single Carotid Body Cells.

The carotid body is the main arterial chemoreceptor in mammals that mediates the cardiorespiratory reflexes activated by acute hypoxia. Here we describe the protocols followed in our laboratory to study responsiveness to hypoxia of single, enzymatically dispersed, glomus cells monitored by microfluorimetry and the patch-clamp technique.