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Vasodilation in response to low oxygen (O2) tension (hypoxic vasodilation) is an essential homeostatic response of systemic arteries that facilitates O2 supply to tissues according to demand. However, how blood vessels react to O2 deficiency is not well understood. A common belief is that arterial myocytes are O2-sensitive. Supporting this concept, it has been shown that the activity of myocyte L-type Ca2+channels, the main ion channels responsible for vascular contractility, is reversibly inhibited by hypoxia, although the underlying molecular mechanisms have remained elusive. Here, we show that genetic or pharmacological disruption of mitochondrial electron transport selectively abolishes O2 modulation of Ca2+ channels and hypoxic vasodilation. Mitochondria function as O2 sensors and effectors that signal myocyte Ca2+ channels due to constitutive Hif1α-mediated expression of specific electron transport subunit isoforms. These findings reveal the acute O2-sensing mechanisms of vascular cells and may guide new developments in vascular pharmacology. Hypoxia inhibits the activity of calcium channels in arterial myocytes by unknown mechanisms and contributes to arterial vasodilation. Here, the authors show that myocyte mitochondria are essential for sensing acute hypoxia and generate signals (NADH and H2O2) that modulate membrane calcium channels. [ABSTRACT FROM AUTHOR]

Background [K.sup.+] channels of the TASK family are believed to participate in sensory transduction by chemoreceptor (glomus) cells of the carotid body (CB). However, studies on the systemic CB-mediated ventilatory response to hypoxia and hypercapnia in TASK1- and/or TASK3-deficient mice have yielded conflicting results. We have characterized the glomus cell phenotype of TASK-null mice and studied the responses of individual cells to hypoxia and other chemical stimuli. CB morphology and glomus cell size were normal in wild-type as well as in [TASK1.sup.-/-] or double [TASK1/3.sup.-/-] mice. Patch-clamped TASK1/3-null glomus cells had significantly higher membrane resistance and less hyperpolarized resting potential than their wild-type counterpart. These electrical parameters were practically normal in [TASK1.sup.-/-] cells. Sensitivity of background currents to changes of extracellular pH was drastically diminished in TASK1/3-null cells. In contrast with these observations, responsiveness to hypoxia or hypercapnia of either [TASK1.sup.-/-] or double [TASK1/3.sup.-/-] cells, as estimated by the amperometric measurement of catecholamine release, was apparently normal. TASK1/3 knockout cells showed an enhanced secretory rate in basal (normoxic) conditions compatible with their increased excitability. Responsiveness to hypoxia of TASK1/3-null cells was maintained after pharmacological blockade of maxi-[K.sup.+] channels. These data in the TASK-null mouse model indicate that TASK3 channels contribute to the background [K.sup.+] current in glomus cells and to their sensitivity to external pH. They also suggest that, although TASK1 channels might be dispensable for [O.sub.2]/C[O.sub.2] sensing in mouse CB cells, TASK3 channels (or TASK1/3 heteromers) could mediate hypoxic depolarization of normal glomus cells. The ability of [TASK1/3.sup.-/-] glomus cells to maintain a powerful response to hypoxia even after blockade of maxi-[K.sup.+] channels, suggests the existence of multiple sensor and/or effector mechanisms, which could confer upon the cells a high adaptability to maintain their chemosensory function. doi/10.1085/jgp.200910302

Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant maxi-[K.sup.+] channels and has been proposed to be the acute [O.sub.2] sensor in the carotid body (CB). We have tested the physiological contribution of this enzyme to [O.sub.2] sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype characterized by organ growth and alteration in the expression of stress-dependent genes, including the maxi-[K.sup.+] channel [alpha]-subunit. However, sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their control littermates. Moreover, the response to hypoxia in mouse and rat CB cells was maintained after blockade of maxi-[K.sup.+] channels with iberiotoxin. Hypoxia responsiveness of the adrenal medulla (AM) (another acutely responding [O.sub.2]-sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that redox disregulation resulting from HO-2 deficiency affects maxi-[K.sup.+] channel gene expression but it does not alter the intrinsic [O.sub.2] sensitivity of CB or AM cells. Therefore, HO-2 is not a universally used acute [O.sub.2] sensor.

The Drosophila mushroom bodies (MBs), paired brain structures composed of vertical and medial lobes, achieve their final organization at metamorphosis. The alpha lobe absent (ala) mutant randomly lacks either the vertical lobes or two of the median lobes. We characterize the ala axonal phenotype at the single-cell level, and show that the ala mutation affects Drosophila ethanolamine (Etu) kinase activity and induces Etn accumulation. Etn kinase is overexpressed in almost all cancer cells. We demonstrate that this enzymatic activity is required in MB neuroblasts to allow a rapid rate of cell division at metamorphosis, linking Etn kinase activity with mitotic progression. Tight control of the pace of neuroblast division is therefore crucial for completion of the developmental program in the adult brain. Keywords: Ethanolamine kinase; alpha lobes absent; Mushroom body; Drosophila; Neuroblast; Mitosis