Depth distribution and mechanism of changes in extracellular K+ and Ca2+ concentrations in the hippocampus

1982 ◽  
Vol 60 (12) ◽  
pp. 1658-1671 ◽  
Author(s):  
K. Krnjević ◽  
M. E. Morris ◽  
R. J. Reiffenstein ◽  
N. Ropert

In the CA1 area of the hippocampus of urethane-anaesthetized rats, the greatest Δ[K+]o and Δ[Ca2+]o evoked by repetitive fimbrial – commissural stimulation were always found in the pyramidal cell layer; but there were large increases in [K+]o over a wide range of depth, whereas a major fall in [Ca2+]o was localized almost exclusively to the level of the pyramidal layer. A sustained focal negative potential was also evoked by fimbrial stimulation; it resembled Δ[K+]o in time course and depth distribution and therefore probably reflected cellular depolarization caused by increased [K+]o. The close correlation between Δ[Ca2+]o and Δ[K+]o and the appearance of population spikes (especially in bursts of three to four spikes) indicate that pyramidal cell firing and corresponding K-outward and Ca-inward currents are mainly responsible for the accumulation of [Formula: see text] and the depletion of [Formula: see text]. In CA3 pyramidal areas, Δ[K+]o and Δ[Ca2+]o were comparable in magnitude and distribution to changes seen in CA1, but they occurred after a longer latency, and the major Δ[Ca2+]o had a longer duration, consistent with a more prolonged Ca2+ current.

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732110227
Author(s):  
Friederike Held ◽  
Sudhakar Reddy Kalluri ◽  
Achim Berthele ◽  
Ana-Katharina Klein ◽  
Markus Reindl ◽  
...  

Background Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab. Objective To investigate the seroprevalence of MOG-Ab under consideration of demographics, disease entities and time course in a large cohort of unselected neurological patients. Methods Blood samples of 2.107 consecutive adult neurologic patients admitted to our department between 2016-2017 were tested for MOG-Ab using a cell-based assay. MOG-Ab persistence was analyzed in follow-up samples. External validation was performed in two independent laboratories. Results We found MOG-Ab in 25 of 2.107 (1.2%) patients. High antibody ratios were mostly associated with NMOSD and MOG-AD phenotype (5/25). Low ratios occurred in a wide range of neurological diseases, predominantly in other demyelinating CNS diseases (5/25) and stroke (6/25). MOG-Ab persistence over time was not confined to NMOSD and MOG-AD phenotype. Conclusion The present study demonstrates the occurrence of MOG-Ab in a wide range of neurological diseases. Only high MOG-Ab ratios were associated with a defined clinical phenotype, but low MOG-Ab ratios were not. The diagnostic value of low MOG-Ab is thus highly limited.


1979 ◽  
Vol 47 (6) ◽  
pp. 1228-1233 ◽  
Author(s):  
D. S. Simon ◽  
J. F. Murray ◽  
N. C. Staub

We evaluated the attenuation of the 122 keV gamma ray of cobalt-57 across the thorax of anesthetized dogs as a method for following the time course of lung water changes in acute pulmonary edema induced by either increased microvascular permeability or increased microvascular hydrostatic pressure. The gamma rays traversed the thorax centered on the seventh rib laterally where the lung mass in the beam path was greatest. Calibration measurements in isolated lung lobes demonstrated the high sensitivity and inherent accuracy of the method over a wide range of lung water contents. In control dogs reproducibility averaged +/-3%. Increased permeability edema led to large rapid increases in the transthoracic gamma ray attenuation (TGA), while increased pressure caused an immediate, modest increase in TGA (vascular congestion) followed by a slow further increase over 2 h. There was a fairly good correlation between the increase in extravascular lung water and the change in TGA. The method is simple, safe, and noninvasive and appears to be useful for following the time course of lung water accumulation in generalized lung edema in anesthetized animals.


2011 ◽  
Vol 22 (7) ◽  
pp. 1487-1497 ◽  
Author(s):  
L. Llado-Pelfort ◽  
N. Santana ◽  
V. Ghisi ◽  
F. Artigas ◽  
P. Celada

2008 ◽  
Vol 9 (S1) ◽  
Author(s):  
A Yadav ◽  
Christina M Weaver ◽  
Yuan Z Gao ◽  
Jennifer I Luebke ◽  
Susan L Wearne

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Daisuke Kase ◽  
Keiji Imoto

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels were first reported in heart cells and are recently known to be involved in a variety of neural functions in healthy and diseased brains. HCN channels generate inward currents when the membrane potential is hyperpolarized. Voltage dependence of HCN channels is regulated by intracellular signaling cascades, which contain cyclic AMP, PIP2, and TRIP8b. In addition, voltage-gated potassium channels have a strong influence on HCN channel activity. Because of these funny features, HCN channel currents, previously called funny currents, can have a wide range of functions that are determined by a delicate balance of modulatory factors. These multifaceted features also make it difficult to predict and elucidate the functional role of HCN channels in actual neurons. In this paper, we focus on the impacts of HCN channels on neural activity. The functions of HCN channels reported previously will be summarized, and their mechanisms will be explained by using numerical simulation of simplified model neurons.


1986 ◽  
Vol 87 (6) ◽  
pp. 857-884 ◽  
Author(s):  
J R Hume ◽  
A Uehara

The objective of these experiments was to test the hypothesis that the "creep currents" induced by Na loading of single frog atrial cells (Hume, J. R., and A. Uehara. 1986. Journal of General Physiology. 87:833) may be generated by an electrogenic Na/Ca exchanger. Creep currents induced by Na loading were examined over a wide range of membrane potentials. During depolarizing voltage-clamp pulses, outward creep currents were observed, followed by inward creep currents upon the return to the holding potential. During hyperpolarizing voltage-clamp pulses, creep currents of the opposite polarity were observed: inward creep currents were observed during the pulses, followed by outward creep currents upon the return to the holding potential. The current-voltage relations for inward and outward creep currents in response to depolarizing or hyperpolarizing voltage displacements away from the holding potential all intersect the voltage axis at a common potential, which indicates that inward and outward creep currents may have a common reversal potential under equilibrium conditions and may therefore be generated by a common mechanism. Measurements of inward creep currents confirm that voltage displacements away from the holding potential rapidly alter equilibrium conditions. Current-voltage relationships of inward creep currents after depolarizing voltage-clamp pulses are extremely labile and depend critically upon the amplitude and duration of outward creep currents elicited during preceding voltage-clamp pulses. An optical monitor of mechanical activity in single cells revealed (a) a similar voltage dependence for the outward creep currents induced by Na loading and tonic contraction, and (b) a close correlation between the time course of the decay of the inward creep current and the time course of mechanical relaxation. A mathematical model of electrogenic Na/Ca exchange (Mullins, L.J. 1979. Federation Proceedings. 35:2583; Noble, D. 1986. Cardiac Muscle. 171-200) can adequately account for many of the properties of creep currents. It is concluded that creep currents in single frog atrial cells may be attributed to the operation of an electrogenic Na/Ca exchange mechanism.


1981 ◽  
Vol 194 (1) ◽  
pp. 187-192 ◽  
Author(s):  
E H Mürer ◽  
K Davenport ◽  
E Siojo ◽  
H J Day

The purpose of this study was to investigate the response of human blood platelets to fluoride at different pH. The results were as follows. (1) Fluoride induced secretion faster and at a lower concentration when pH was lowered. (2) Platelets exposed to 2 mM-fluoride at 0 degrees C at pH 5.3 underwent secretion when first pH and then temperature was raised, although no secretion was seen at 2 mM-fluoride concentration in the absence of the preincubation at low pH. (3) The concentration of [14C]ATP in platelets decreased steeply in response to fluoride before induction of secretion. Addition of antimycin blocked or partly inhibited secretion. Fluoride thus exerts an inhibitory effect on platelet glycolysis before induction of secretion. (4) Fluoride accumulated in the platelet pellet by a time course that preceded secretion. The accumulation was faster and greater at pH 6 than at 7.4. These four points are taken as indirect evidence that fluoride has to penetrate to the interior of the platelet to induce secretion. The activation takes place over a wide range of acid pH in contrast with induction of platelet function via the outside of the plasma membrane. In addition evidence is presented that the salvage pathway may under special circumstances play an important role in the re-synthesis of platelet adenine nucleotides.


2015 ◽  
Vol 146 (1) ◽  
pp. 15-36 ◽  
Author(s):  
Giovanni Gonzalez-Gutierrez ◽  
Claudio Grosman

The superfamily of pentameric ligand-gated ion channels (pLGICs) is unique among ionotropic receptors in that the same overall structure has evolved to generate multiple members with different combinations of agonist specificities and permeant-ion charge selectivities. However, aside from these differences, pLGICs have been typically regarded as having several invariant functional properties. These include pore blockade by extracellular quaternary-ammonium cations in the micromolar-to-millimolar concentration range (in the case of the cation-selective members), and a gain-of-function phenotype, which manifests as a slower deactivation time course, as a result of mutations that reduce the hydrophobicity of the transmembrane pore lining. Here, we tested this notion on three distantly related cation-selective members of the pLGIC superfamily: the mouse muscle nicotinic acetylcholine receptor (nAChR), and the bacterial GLIC and ELIC channels. Remarkably, we found that, whereas low millimolar concentrations of TMA+ and TEA+ block the nAChR and GLIC, neither of these two quaternary-ammonium cations blocks ELIC at such concentrations; instead, both carry measurable inward currents when present as the only cations on the extracellular side. Also, we found that, whereas lidocaine binding speeds up the current-decay time courses of the nAChR and GLIC in the presence of saturating concentrations of agonists, the binding of lidocaine to ELIC slows this time course down. Furthermore, whereas mutations that reduce the hydrophobicity of the side chains at position 9′ of the M2 α-helices greatly slowed the deactivation time course of the nAChR and GLIC, these mutations had little effect—or even sped up deactivation—when engineered in ELIC. Our data indicate that caution should be exercised when generalizing results obtained with ELIC to the rest of the pLGICs, but more intriguingly, they hint at the possibility that ELIC is a representative of a novel branch of the superfamily with markedly divergent pore properties despite a well-conserved three-dimensional architecture.


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