Depolarizing response of rat parathyroid cells to divalent cations

Membrane potentials were recorded from rat parathyroid glands continuously perfused in vitro. At 1 .5 mM external Ca", the resting potential averages -73 ± 5 mV (mean ± SD, n = 66). On exposure to 2.5 mM Ca", the cells depolarize reversibly to a potential of -34 ± 8 mV (mean ± SD). Depolarization to this value is complete in ^-2-4 min, and repolarization on return to 1 .5 mM Ca" takes about the same time. The depolarizing action of high Ca" is mimicked by all divalent cations tested, with the following order of effectiveness: Ca" > Sr" > Mg" > Ba++ for alkali-earth metals, and Ca" > Cd++ > Mn++ > Co' > Zn++ for transition metals . Input resistance in 1 .5 mM Ca" was 24 .35 ± 14 MQ (mean ± SD) and increased by an average factor of 2.43 ± 0.8 after switching to 2.5 mM Ca++. The low value of input resistance suggests that cells are coupled by low-resistance junctions. Theresting potential in low Ca' is quite insensitive to removal of external Na+ or Cl-, but very sensitive to changes in external K+. Cells depolarize by 61 mV for a 10=fold increase in external K+. In high Ca++, membrane potential is less sensitive to an increase in external K+ and is unchanged by increasing K+ from 5 to 25 mM. Depolarization evoked by high Ca' may be slowed, but is unchanged in amplitude by removal of external Na+ or Cl-. Organic (13600) and inorganic (Co++, Cd++, and Mn++) blockers of the Ca' channels do not interfere with the electrical response to Ca" changes. Our results show remarkable parallels to previous observations on the control ofparathormone (PTH) release by Ca". They suggest an association between membrane voltage and secretion that is very unusual: parathyroid cells secrete when fully polarized, and secrete less when depolarized. The extraordinary sensitivity of parathyroid cells to divalent cations leads us to hypothesize the existence in their membranes ofa divalent cation receptor that controls membrane permeability (possibly to K+) and PTH secretion

Effect of hypoxia on lung gene expression and proteomic profile: insights into the pulmonary surfactant response

Exposure of lung to hypoxia has been previously reported to be associated with significant alterations in the protein content of bronchoalveolar lavage (BAL) and lung tissue. In the present work we have used a proteomic approach to describe the changes in protein complement induced by moderate long-term hypoxia (rats exposed to 10% O2 for 72h) in BAL and lung tissue, with a special focus on the proteins associated with pulmonary surfactant, which could indicate adaptation of this system to limited oxygen availability. The analysis of the general proteomic profile indicates a hypoxia-induced increase in proteins associated with inflammation both in lavage and lung tissue. Analysis at mRNA and protein levels revealed no significant changes induced by hypoxia on the content in surfactant proteins or their apparent oligomeric state. In contrast, we detected a hypoxia-induced significant increase in the expression and accumulation of hemoglobin in lung tissue, at both mRNA and protein levels, as well as an accumulation of hemoglobin both in BAL and associated with surface-active membranes of the pulmonary surfactant complex. Evaluation of pulmonary surfactant surface activity from hypoxic rats showed no alterations in its spreading ability, ruling out inhibition by increased levels of serum or inflammatory proteins.Ministerio de Ciencia BIO2012-30733Ministerio de Ciencia CSD2007-00010Gobierno de la Comunidad de Madrid S2009MAT-1507National Institutes of Health NIH HL3478

Low pO2 selectively inhibits K channel activity in chemoreceptor cells of the mammalian carotid body

The hypothesis that changes in environmental O2 tension (pO2) could affect the ionic conductances of dissociated type I cells of the carotid body was tested. Cells were subjected to whole-cell patch clamp and ionic currents were recorded in a control solution with normal pO2 (pO2 = 150 mmHg) and 3-5 min after exposure to the same solution with a lower pO2. Na and Ca currents were unaffected by lowering pO2 to 10 mmHg, however, in all cells studied (n = 42) exposure to hypoxia produced a reversible reduction of the K current. In 14 cells exposed to a pO2 of 10 mmHg peak K current amplitude decreased to 35 +/- 8% of the control value. The effect of low pO2 was independent of the internal Ca2+ concentration and was observed in the absence of internal exogenous nucleotides. Inhibition of K channel activity by hypoxia is a graded phenomenon and in the range between 70 and 120 mmHg, which includes normal pO2 values in arterial blood, it is directly correlated with pO2 levels. Low pO2 appeared to slow down the activation time course of the K current but deactivation kinetics seemed to be unaltered. Type I cells subjected to current clamp generate large Na- and Ca-dependent action potentials repetitively. Exposure to low pO2 produces a 4-10 mV increase in the action potential amplitude and a faster depolarization rate of pacemaker potentials, which leads to an increase in the firing frequency. Repolarization rate of individual action potentials is, however, unaffected, or slightly increased. The selective inhibition of K channel activity by low pO2 is a phenomenon without precedents in the literature that explains the chemoreceptive properties of type I cells. The nature of the interaction of molecular O2 with the K channel protein is unknown, however, it is argued that a hemoglobin-like O2 sensor, perhaps coupled to a G protein, could be involved

Ionic currents in dispersed chemoreceptor cells of the mammalian carotid body

Ionic currents of enzymatically dispersed type I and type II cells of the carotid body have been studied using the whole cell variant of the patch-clamp technique. Type II cells only have a tiny, slowly activating outward potassium current. By contrast, in every type I chemoreceptor cell studied we found (a) sodium, (b) calcium, and (c) potassium currents. (a) The sodium current has a fast activation time course and an activation threshold at approximately -40 mV. At all voltages inactivation follows a single exponential time course. The time constant of inactivation is 0.67 ms at 0 mV. Half steady state inactivation occurs at a membrane potential of approximately -50 mV. (b) The calcium current is almost totally abolished when most of the external calcium is replaced by magnesium. The activation threshold of this current is at approximately -40 mV and at 0 mV it reaches a peak amplitude in 6-8 ms. The calcium current inactivates very slowly and only decreases to 27% of the maximal value at the end of 300-ms pulses to 40 mV. The calcium current was about two times larger when barium ions were used as charge carriers instead of calcium ions. Barium ions also shifted 15-20 mV toward negative voltages the conductance vs. voltage curve. Deactivation kinetics of the calcium current follows a biphasic time course well fitted by the sum of two exponentials. At -80 mV the slow component has a time constant of 1.3 +/- 0.4 ms whereas the fast component, with an amplitude about 20 times larger than the slow component, has a time constant of 0.16 +/- 0.03 ms. These results suggest that type I cells have predominantly fast deactivating calcium channels. The slow component of the tails may represent the activity of a small population of slowly deactivating calcium channels, although other possibilities are considered. (c) Potassium current seems to be mainly due to the activity of voltage-dependent potassium channels, but a small percentage of calcium-activated channels may also exist. This current activates slowly, reaches a peak amplitude in 5-10 ms, and thereafter slowly inactivates. Inactivation is almost complete in 250-300 ms. The potassium current is reversibly blocked by tetraethylammonium. Under current-clamp conditions type I cells can spontaneously fire large action potentials. These results indicate that type I cells are excitable and have a variety of ionic conductances. We suggest a possible participation of these conductances in chemoreception

Editorial: Hypoxia and Cardiorespiratory Control

To maintain adequate oxygen levels in the body, which is essential for a healthy life, the respiratory and cardiovascular systems play vitally important roles. When the oxygen content is insufficient, i.e., when hypoxia is loaded, respiratory and cardiovascular systems respond to restore, compensate, or adapt to hypoxia, e.g., by increasing ventilation and blood flow to maintain oxygen transport to vital organs. Traditionally, it has been thought that hypoxia is detected solely by carotid and aortic bodies, i.e., by peripheral chemoreceptors, and information from the peripheral chemoreceptors is transmitted to respiratory and cardiovascular centers in the brainstem whose respiratory and cardiovascular neural outputs are regulated. However, recent progress in neurophysiology has clarified that there are hypoxia-sensors not only in the periphery but also in the central nervous system. Hypoxia also affects the vascular system causing atherosclerosis and pulmonary hypertension and impairs blood glucose regulation that also facilitates atherosclerosis. The effects of hypoxia on vital organs and tissues vary depending on the modality of hypoxia exposure, i.e., acute, chronically sustained, or intermittent hypoxia. Although these issues have been vigorously investigated, the underlying mechanisms are yet to be unraveled. Likewise, long-range consequences for organ and tissue functions affected by hypoxia have not been fully elucidated. In the article collection of this Research Topic, a series of studies report the latest and most notable pathophysiological findings that are categorized into four areas: respiratory control, glucose metabolism, pulmonary hypertension, and sympathetic nervous system activation. The articles attempt to clarify many of the unsolved issues summarized below. (Introduction

Age-Mediated Transcriptomic Changes in Adult Mouse Substantia Nigra

Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease (PD). Until now, molecular mechanisms behind SNpc aging have not been fully investigated using high throughput techniques. Here, we show early signs of aging in SNpc, which are more evident than in ventral tegmental area (VTA), a region adjacent to SNpc but less affected in PD. Aging-associated early changes in transcriptome were investigated comparing late middle-aged (18 months old) to young (2 months old) mice in both SNpc and VTA. A meta-analysis of published microarray studies allowed us to generate a common >transcriptional signature> of the aged (≥ 24 months old) mouse brain. SNpc of late-middle aged mice shared characteristics with the transcriptional signature, suggesting an accelerated aging in SNpc. Age-dependent changes in gene expression specific to SNpc were also observed, which were related to neuronal functions and inflammation. Future studies could greatly help determine the contribution of these changes to SNpc aging. These data help understand the processes underlying SNpc aging and their potential contribution to age-related disorders like PD. © 2013 Gao et al.This work was funded by Spanish Ministry of Science and Education, Andalusian Government, and “Marcelino Botín” Foundation. “CIBERNED” (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) was funded by the Spanish “Carlos III” Institute of Health. LME was supported by the Spanish “Carlos III” Institute of Health. Support from the Spanish Ministry of Science and Education for MHF (“FPI” predoctoral fellowship) is also acknowledged.Peer Reviewe

Nuclear currents based on the integral form of the continuity equation

We present an approach to obtain new forms of the nuclear electromagnetic current, which is based on an integral form of the continuity equation. The procedure can be used to restore current conservation in model calculations in which the continuity equation is not verified. Besides, it provides, as a particular result, the so-called Siegert's form of the nuclear current, first obtained by Friar and Fallieros by extending Siegert's theorem to arbitrary values of the momentum transfer. The new currents are explicitly conserved and permit a straightforward analysis of their behavior at both low and high momentum transfers. The results are illustrated with a simple nuclear model which includes a harmonic oscillator mean potential.Comment: 19 pages, revtex, plus 2 PS figure

Measurement of the LT-asymmetry in \pi^0 electroproduction at the energy of the \Delta (1232) resonance

The reaction p(e,e'p)pi^0 has been studied at Q^2=0.2 (GeV/c)^2 in the region of W=1232 MeV. From measurements left and right of q, cross section asymmetries \rho_LT have been obtained in forward kinematics \rho_LT(\theta_\pi^0=20deg) = (-11.68 +/- 2.36_stat +/- 2.36_sys)$ and backward kinematics \rho_LT(\theta_\pi^0=160deg) =(12.18 +/- 0.27_stat +/- 0.82_sys). Multipole ratios \Re(S_1+^* M_1+)/|M_1+|^2 and \Re(S_0+^* M_1+)/|M_1+|^2 were determined in the framework of the MAID2003 model. The results are in agreement with older data. The unusally strong negative \Re(S_0+^* M_1+)/|M_1+|^2 required to bring also the result of Kalleicher et al. in accordance with the rest of the data is almost excluded.Comment: 7 pages, 7 figures, 4 tables. Changed content. Accepted for publication in EPJ

First measurements of the ^16O(e,e'pn)^14N reaction

This paper reports on the first measurement of the ^16O(e,e'pn)^14N reaction. Data were measured in kinematics centred on a super-parallel geometry at energy and momentum transfers of 215 MeV and 316 MeV/c. The experimental resolution was sufficient to distinguish groups of states in the residual nucleus but not good enough to separate individual states. The data show a strong dependence on missing momentum and this dependence appears to be different for two groups of states in the residual nucleus. Theoretical calculations of the reaction using the Pavia code do not reproduce the shape or the magnitude of the data.Comment: 10 pages, 11 figures, 2 tables, Accepted for publication in EPJ