Muscle velocity recovery cycles: a tool to study muscle membrane properties in vivo

2009 ◽  
Vol 40 (01) ◽  
Author(s):  
H Bostock ◽  
WJ Z'Graggen
Author(s):  
Agnes Witt ◽  
Hugh Bostock ◽  
Werner J. Z'Graggen ◽  
S. Veronica Tan ◽  
Alexander Gramm Kristensen ◽  
...  

2016 ◽  
Vol 54 (2) ◽  
pp. 249-257 ◽  
Author(s):  
S. Veronica Tan ◽  
Werner J. Z'graggen ◽  
Delphine Boërio ◽  
Christopher Turner ◽  
Michael G. Hanna ◽  
...  

1982 ◽  
Vol 243 (6) ◽  
pp. E512-E521 ◽  
Author(s):  
R. L. Ruff ◽  
D. Martyn ◽  
A. M. Gordon

We explored the possibility that glucocorticoid-induced muscle weakness and atrophy resulted from impaired muscle membrane excitability. Male Sprague-Dawley rats received intramuscular injections of dexamethasone, cortisone acetate (equivalent anti-inflammatory doses), or saline for up to 28 days. Temporal patterns of change in muscle mass, twitch and tetanic tension, and membrane potential, cable parameters, and excitability were studied in vitro in the extensor digitorum longus (EDL), soleus (SOL), omohyoid (OMO), caudofemoralis (CF), and the sternomastoid muscles (membrane potential only). the membrane properties of EDL fibers were also studied in vivo (pentobarbital anesthesia). The relative severity of atrophy was OMO greater than CF greater than EDL greater than SOL. Reduction in twitch or tetanic tension never preceded atrophy. The twitch and tetanic tension (per g muscle) increased with glucocorticoid treatment. There were no significant changes in the time course of the twitch or tetanus. Dexamethasone produced more severe atrophy and force reduction than did cortisone acetate. Glucocorticoid treatment produced a depolarization of EDL muscle fibers measured in vitro at 23 degrees C, but this did not appear to be physiologically significant because EDL fibers studied in vivo were not depolarized and had normal action potential amplitudes and thresholds. Glucocorticoid treatment did not change the membrane resistance or capacitance. We conclude that glucocorticoid treatment did not produce muscle weakness by impairing sarcolemmal excitability or excitation-contraction coupling, but that the weakness resulted from muscle atrophy.


Critical Care ◽  
2009 ◽  
Vol 13 (Suppl 1) ◽  
pp. P111
Author(s):  
WJ Z'Graggen ◽  
L Brander ◽  
D Tuchscherer ◽  
A Brunello ◽  
C Passath ◽  
...  

2017 ◽  
Vol 57 (4) ◽  
pp. 586-594 ◽  
Author(s):  
S. Veronica Tan ◽  
Werner J. Z'Graggen ◽  
Michael G. Hanna ◽  
Hugh Bostock

2011 ◽  
Vol 122 (4) ◽  
pp. 834-841 ◽  
Author(s):  
W.J. Z’Graggen ◽  
L. Brander ◽  
D. Tuchscherer ◽  
O. Scheidegger ◽  
J. Takala ◽  
...  

1999 ◽  
Vol 16 (3) ◽  
pp. 557-570 ◽  
Author(s):  
HONGJING TAN ◽  
RICHARD D. MOONEY ◽  
ROBERT W. RHOADES

Intracellular recording techniques were used to evaluate the effects of norepinephrine (NE) on the membrane properties of superficial layer (stratum griseum superficiale and stratum opticum) superior colliculus (SC) cells. Of the 207 cells tested, 44.4% (N = 92) were hyperpolarized by ≥3 mV and 8.7% (N = 18) were depolarized by ≥3 mV by application of NE. Hyperpolarization induced by NE was dose dependent (EC50 = 8.1 μM) and was associated with decreased input resistance and outward current which had a reversal potential of −94.0 mV. Depolarization was associated with a very slight rise in input resistance and had a reversal potential of −93.1 mV for the single cell tested. Pharmacologic experiments demonstrated that isoproterenol, dobutamine, and p-aminoclonidine all hyperpolarized SC cells. These results are consistent with the conclusion that NE-induced hyperpolarization of SC cells is mediated by both α2 and β1 adrenoceptors. The α1 adrenoceptor agonists, methoxamine and phenylephrine, depolarized 35% (6 of 17) of the SC cells tested by ≥3 mV. Most of the SC cells tested exhibited responses indicative of expression of more than one adrenoceptor. Application of p-aminoclonidine or dobutamine inhibited transsynaptic responses in SC cells evoked by electrical stimulation of optic tract axons. Inhibition of evoked responses by these agents was usually, but not invariably, associated with a hyperpolarization of the cell membrane and a reduction in depolarizing potentials evoked by application of glutamate. The present in vitro results are consistent with those of the companion in vivo study which suggested that NE-induced response suppression in superficial layer SC neurons was primarily postsynaptic and chiefly mediated by both α2 and β1 adrenoceptors.


2018 ◽  
Vol 8 (4) ◽  
pp. 38 ◽  
Author(s):  
Kenji Lim ◽  
Chantal Yoon ◽  
Toshifumi Yokota

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive neuromuscular disease prevalent in 1 in 3500 to 5000 males worldwide. As a result of mutations that interrupt the reading frame of the dystrophin gene (DMD), DMD is characterized by a loss of dystrophin protein that leads to decreased muscle membrane integrity, which increases susceptibility to degeneration. CRISPR/Cas9 technology has garnered interest as an avenue for DMD therapy due to its potential for permanent exon skipping, which can restore the disrupted DMD reading frame in DMD and lead to dystrophin restoration. An RNA-guided DNA endonuclease system, CRISPR/Cas9 allows for the targeted editing of specific sequences in the genome. The efficacy and safety of CRISPR/Cas9 as a therapy for DMD has been evaluated by numerous studies in vitro and in vivo, with varying rates of success. Despite the potential of CRISPR/Cas9-mediated gene editing for the long-term treatment of DMD, its translation into the clinic is currently challenged by issues such as off-targeting, immune response activation, and sub-optimal in vivo delivery. Its nature as being mostly a personalized form of therapy also limits applicability to DMD patients, who exhibit a wide spectrum of mutations. This review summarizes the various CRISPR/Cas9 strategies that have been tested in vitro and in vivo for the treatment of DMD. Perspectives on the approach will be provided, and the challenges faced by CRISPR/Cas9 in its road to the clinic will be briefly discussed.


1996 ◽  
Vol 75 (5) ◽  
pp. 2029-2035 ◽  
Author(s):  
R. A. Travagli ◽  
M. Wessendorf ◽  
J. T. Williams

1. The nucleus locus coeruleus (LC) is made up of noradrenergic cells all of which are hyperpolarized by opioids. Recent work has shown that the reversal potential of the opioid-induced current is more negative than the potassium equilibrium potential. The aim of the present study was to determine whether the extent of the dendritic field could contribute to the very negative opioid reversal potential. 2. Individual LC cells were labeled in the brain slice preparation. The number of dendrites found on cells in slices sectioned in the horizontal plane was greater than cells in coronal slices. However, the dimensions of the cell body slices from each plane were not significantly different. 3. The resting conductance of neurons from slices cut in the horizontal plane was significantly larger than in cells from coronal plane. 4. The amplitude of the outward current induced by [Met5]-enkephalin (ME) was larger in cells from horizontal slices and the reversal potential was more negative than that of cells in coronal slices. 5. The results show that the plane of section influences the membrane properties and opioid actions of LC neurons in vitro and suggest that these differences correlate with the numbers of dendrites. The results suggest that in vivo, in addition to intrinsic membrane properties and synaptic inputs, the structural makeup of the nucleus is an important factor in determining the activity.


2000 ◽  
Vol 84 (6) ◽  
pp. 2746-2757 ◽  
Author(s):  
Min Zhou ◽  
Harold K. Kimelberg

Whether astrocytes predominantly express ohmic K+ channels in vivo, and how expression of different K+ channels affects [K+]ohomeostasis in the CNS have been long-standing questions for how astrocytes function. In the present study, we have addressed some of these questions in glial fibrillary acidic protein [GFAP(+)], freshly isolated astrocytes (FIAs) from CA1 and CA3 regions of P7–15 rat hippocampus. As isolated, these astrocytes were uncoupled allowing a higher resolution of electrophysiological study. FIAs showed two distinct ion current profiles, with neither showing a purely linear I-V relationship. One population of astrocytes had a combined expression of outward potassium currents ( I Ka, I Kd) and inward sodium currents ( I Na). We term these outwardly rectifying astrocytes (ORA). Another population of astrocytes is characterized by a relatively symmetric potassium current pattern, comprising outward I Kdr, I Ka, and abundant inward potassium currents ( I Kin), and a larger membrane capacitance ( C m ) and more negative resting membrane potential (RMP) than ORAs. We term these variably rectifying astrocytes (VRA). The I Kin in 70% of the VRAs was essentially insensitive to Cs+, while I Kin in the remaining 30% of VRAs was sensitive. The I Ka of VRAs was most sensitive to 4-aminopyridine (4-AP), while I Kdr of ORAs was more sensitive to tetraethylammonium (TEA). ORAs and VRAs occurred approximately equally in FIAs isolated from the CA1 region (52% ORAs versus 48% VRAs), but ORAs were enriched in FIAs isolated from the CA3 region (71% ORAs versus 29% VRAs), suggesting an anatomical segregation of these two types of astrocytes within the hippocampus. VRAs, but not ORAs, showed robust inward currents in response to an increase in extracellular K+ from 5 to 10 mM. As VRAs showed a similar current pattern and other passive membrane properties (e.g., RMP, R in) to “passive astrocytes”in situ (i.e., these showing linear I-V curves), such passive astrocytes possibly represent VRAs influenced by extensive gap-junction coupling in situ. Thus, our data suggest that, at least in CA1 and CA3 regions from P7–15 rats, there are two classes of GFAP(+) astrocytes which possess different K+ currents. Only VRAs seem suited to uptake of extracellular K+ via I Kin channels at physiological membrane potentials and increases of [K+]o. ORAs show abundant outward potassium currents with more depolarized RMP. Thus VRAs and ORAs may cooperate in vivo for uptake and release of K+, respectively.


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