Many cell types have significant negative resting membrane potentials (RMPs) resulting from the activity of potassium-selective and chloride-selective ion channels. In excitable cells, such as neurones, rapid changes in membrane permeability underlie the generation of action potentials. Chondrocytes have less negative RMPs and the role of the RMP is not clear. Here we examine the basis of the chondrocyte RMP and possible physiological benefits. We demonstrate that maintenance of the chondrocyte RMP involves gadolinium-sensitive cation channels. Pharmacological inhibition of these channels causes the RMP to become more negative (100 µM gadolinium: ΔVm = −30 ± 4 mV). Analysis of the gadolinium-sensitive conductance reveals a high permeability to calcium ions (PCa/PNa ≈80) with little selectivity between monovalent ions; similar to that reported elsewhere for TRPV5. Detection of TRPV5 by PCR and immunohistochemistry and the sensitivity of the RMP to the TRPV5 inhibitor econazole (ΔVm = −18 ± 3 mV) suggests that the RMP may be, in part, controlled by TRPV5. We investigated the physiological advantage of the relatively positive RMP using a mathematical model in which membrane stretch activates potassium channels allowing potassium efflux to oppose osmotic water uptake. At very negative RMP potassium efflux is negligible, but at more positive RMP it is sufficient to limit volume increase. In support of our model, cells clamped at −80 mV and challenged with a reduced osmotic potential swelled approximately twice as much as cells at +10 mV. The positive RMP may be a protective adaptation that allows chondrocytes to respond to the dramatic osmotic changes, with minimal changes in cell volume. J. Cell. Physiol. 226: 2979–2986, 2011. © 2011 Wiley-Liss, Inc.
Japanese knotweed, Fallopia japonica var. japonica, causes significant disruption to natural and managed habitats, and provides a model for the control of invasive rhizome-forming species. The socioeconomic impacts of the management of, or failure to manage, Japanese knotweed are enormous, annually costing hundreds of millions of pounds sterling (GBP£) in the UK alone. Our study describes the most extensive field-based assessment of F. japonica control treatments undertaken, testing the largest number of physical and/or chemical control treatments (19 in total) in replicated 225 m 2 plots over 3 years. Treatments focused on phenology, resource allocation and rhizome source-sink relationships to reduce the ecological impacts of controlling F. japonica. While no treatment completely eradicated F. japonica, a multiple-stage glyphosate-based treatment approach provided greatest control. Increasing herbicide dose did not improve knotweed control, but treatments that maximised glyphosate coverage, e.g., spraying versus stem injection, and exploited phenological changes in rhizome source-sink relationships caused the greatest reduction of basal cover and stem density after 3 years. When designing management Electronic supplementary material The online version of this article (
The Na ϩ /K ϩ ATPase (NKA) is an essential membrane protein underlying the membrane potential in excitable cells. Transmembrane ion transport is performed by the catalytic ␣ subunits (␣1-4). The predominant subunits in neurons are ␣1 and ␣3, which have different affinities for Na ϩ and K ϩ , impacting on transport kinetics. The exchange rate of Na ϩ /K ϩ markedly influences the activity of the neurons expressing them. We have investigated the distribution and function of the main isoforms of the ␣ subunit expressed in the mouse spinal cord. NKA␣1 immunoreactivity (IR) displayed restricted labeling, mainly confined to large ventral horn neurons and ependymal cells. NKA␣3 IR was more widespread in the spinal cord, again being observed in large ventral horn neurons, but also in smaller interneurons throughout the dorsal and ventral horns. Within the ventral horn, the ␣1 and ␣3 isoforms were mutually exclusive, with the ␣3 isoform in smaller neurons displaying markers of ␥-motoneurons and ␣1 in ␣-motoneurons. The ␣3 isoform was also observed within muscle spindle afferent neurons in dorsal root ganglia with a higher proportion at cervical versus lumbar regions. We confirmed the differential expression of ␣ subunits in motoneurons electrophysiologically in neonatal slices of mouse spinal cord. ␥-Motoneurons were excited by bath application of low concentrations of ouabain that selectively inhibit NKA␣3 while ␣-motoneurons were insensitive to these low concentrations. The selective expression of NKA␣3 in ␥-motoneurons and muscle spindle afferents, which may affect excitability of these neurons, has implications in motor control and disease states associated with NKA␣3 dysfunction.
Modulatory influences on sympathetic nervous system activity are diverse and far reaching, acting at select points in the complex pathways controlling sympathetic outflow to enable subtle changes or more global effects. Changes in the degree of sympathetic neuromodulation can have serious consequences on homeostatic variables such as heart rate, blood pressure and gut motility. At the level of the spinal cord, the sympathetic preganglionic neurons (SPNs) can be modulated by activation of presynaptic GABAB heteroreceptors on glutamatergic terminals and by postsynaptic GABAB receptors. Here we show that a low concentration of the GABAB agonist baclofen (1 μM) attenuated GABAergic inhibitory postsynaptic potentials in SPNs elicited from stimulation of either the central autonomic area or descending fibers in the lateral funiculus. This low baclofen concentration also elicited three categories of postsynaptic response: a large hyperpolarization with a decrease in input resistance, a moderate hyperpolarization with no change in input resistance and no response. Using cesium-loaded, tetraethylammonium chloride containing electrodes (to block potassium conductance), baclofen elicited moderate hyperpolarizations with no change in input resistance in 50% of SPNs; the remainder were unaffected. These modest hyperpolarizations were reduced in Ca2+ free solution or cadmium. Hyperpolarizing responses were also observed in interneurons in the vicinity of SPNs. These studies provide the first evidence for GABAB autoreceptors involved in inhibitory GABAergic transmission onto SPNs and for postsynaptic GABAB receptors on interneurons. The data also indicate that there is heterogeneity in the postsynaptic responses of SPNs.
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