The Concentrations of Calcium Buffering Proteins in Mammalian Cochlear Hair Cells

Hackney, Carole M.; Mahendrasingam, Shanthini; Penn, Andrew C.; Fettiplace, Robert

doi:10.1523/jneurosci.1196-05.2005

Cited by 189 publications

(197 citation statements)

References 61 publications

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“…OM, the beta isoform of parvalbumin, discovered by MacManus (1979) and by Brewer and MacManus (1987) was known until now to be present in adult mammals only in the organ of Corti of the inner ear, in particular in the outer hair cells (Thalmann et al, 1995;Sakaguchi et al, 1998, Hackney et al, 2005. According to our present studies, an extensive system of OM-immunoreactive axons is present in the diencephalon of PV-deficient animals.…”

Section: Discussionsupporting

confidence: 65%

Upregulated expression of oncomodulin, the beta isoform of parvalbumin, in perikarya and axons in the diencephalon of parvalbumin knockout mice

et al. 2010

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Abstract-The calcium-binding proteins parvalbumin, calbindin D-28k, calretinin and calcineurin are present in subsets of GABAergic gigantic calyciform presynaptic terminals of the reticular thalamic nucleus (RTN). Previously it was hypothesized that GABA and calcium-binding proteins including parvalbumin are not only colocalized in the same neuron subpopulation, but that GABA synthesis and parvalbumin expression could be also genetically regulated by a common mechanism. Moreover, parvalbumin expression levels could influence GABA synthesis. For this, we analyzed GABA immunoreactivity in RTN gigantic calyciform presynaptic terminals of parvalbumin-deficient (PV؊/؊) mice. With respect to GABA immunoreactivity we found no differences compared to wild-type animals. However, using a polyclonal parvalbumin antibody raised against full-length rat muscle parvalbumin on brain sections of PV؊/؊ mice, we observed paradoxical parvalbumin immunoreactivity in partly varicose axons in the diencephalon, mainly in the lamina medullaris externa surrounding the thalamus. A detailed immunohistochemical, biochemical and molecular biological analysis revealed this immunoreactivity to be the result of an upregulation of oncomodulin (OM), the mammalian beta isoform of parvalbumin in PV؊/؊ mice. In addition, OM was present in a sparse subpopulation of neurons in the thalamus and in the dentate gyrus. OM expression has not been observed before in neurons of the mammalian brain; its expression was restricted to outer hair cells in the organ of Corti. Our results indicate that the absence of parvalbumin has no major effect on the GABA-synthesizing system in RTN presynaptic terminals excluding a direct effect of parvalbumin on this regulation. However, a likely homeostatic mechanism is induced resulting in the upregulation of OM in selected axons and neuronal perikarya. Our results warrant further detailed investigations on the putative role of OM in the brain.

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Section: Discussionsupporting

confidence: 65%

Upregulated expression of oncomodulin, the beta isoform of parvalbumin, in perikarya and axons in the diencephalon of parvalbumin knockout mice

et al. 2010

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“…The almost identical results in PVϪ/Ϫ and double knockout mice indicate that PV's absence is inducing the morphological alterations. When comparing the properties of CB and PV and their estimated concentration in PC (100 -200 M for both proteins (Maeda et al, 1999;Schmidt et al, 2003b;Hackney et al, 2005), the Ca 2ϩ -binding kinetics appear to be the most distinct feature between the two proteins and are a likely cause for the specific compensation mechanisms induced in PC deficient for either Ca 2ϩ buffer.…”

Section: Discussionmentioning

confidence: 99%

Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells

et al. 2006

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Abstract-The Ca 2؉ -binding proteins parvalbumin (PV) and calbindin D-28k (CB) are key players in the intracellular Ca 2؉ -buffering in specific cells including neurons and have profound effectson spatiotemporal aspects of Ca 2؉ transients. The previously observed increase in mitochondrial volume density in fast-twitch muscle of PV؊/؊ mice is viewed as a specific compensation mechanism to maintain Ca 2؉ homeostasis. Since cerebellar Purkinje cells (PC) are characterized by high expression levels of the Ca 2؉ buffers PV and CB, the question was raised, whether homeostatic mechanisms are induced in PC lacking these buffers. Mitochondrial volume density, i.e. relative mitochondrial mass was increased by 40% in the soma of PV؊/؊ PC. Upregulation of mitochondrial volume density was not homogenous throughout the soma, but was selectively restricted to a peripheral region of 1.5 m width underneath the plasma membrane. Accompanied was a decreased surface of subplasmalemmal smooth endoplasmic reticulum (sPL-sER) in a shell of 0.5 m thickness underneath the plasma membrane. These alterations were specific for the absence of the "slow-onset" buffer PV, since in CB؊/؊ mice neither changes in peripheral mitochondria nor in sPL-sER were observed. This implicates that the morphological alterations are aimed to specifically substitute the function of the slow buffer PV. We propose a novel concept that homeostatic mechanisms of components involved in Ca 2؉ homeostasis do not always occur at the level of similar or closely related molecules. Rather the cell attempts to restore spatiotemporal aspects of Ca 2؉ signals prevailing in the undisturbed (wildtype) situation by subtly fine tuning existing components involved in the regulation of Ca 2؉ fluxes.Key words: calcium-binding, buffers, EF-hand, homeostasis, morphology.Ca 2ϩ ions are such ubiquitous second messengers that meaningful information must be contained in the subtle spatiotemporal aspects of Ca 2ϩ transients. A complex machinery of Ca 2ϩ entry and release systems, mobile and immobile Ca 2ϩ buffers, transient Ca 2ϩ -storage devices and Ca 2ϩ -extrusion systems governs the shape and spreading of intracellular Ca 2ϩ transients (Berridge et al., 2003). Affinities, kinetics of binding and release of Ca 2ϩ ions, the relative mobility and the geometrical distribution of all components, that is, the interplay between these systems finally shapes the spatiotemporal aspects of a Ca 2ϩ signal. Cerebellar Purkinje cells (PC) are characterized by extensive Ca 2ϩ signaling in somata, dendrites and spines elicited by either climbing fiber or parallel fiber stimulation. Following depolarization-evoked rises in the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) in the PC somata, endoplasmic reticulum (ER) and plasma membrane Ca 2ϩ pumps and the Na ϩ -Ca 2ϩ exchanger contribute to PC [Ca 2ϩ ] i clearance (Fierro et al., 1998). Since these systems only accounted for approximately 60% of total Ca 2ϩ clearing, mitochondria were additionally postulated to play a role. These organelles have...

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“…High concentrations of CR (1.2 mM) are also present in tall saccular hair cells of the frog (Edmonds et al 2000). In other cells, calretinin concentration is much lower: approximately 20 mM and 35 mM in rat inner and outer hair cells, respectively (Hackney et al 2005), and 30 -40 mM in mouse cerebellar granule cells (Gall et al 2003). The concentration of CB-D28k is 150 -360 mM in Purkinje cells (for a review, see Schwaller et al 2002), and 40 -50 mM in mature hippocampal dentate gyrus granule cells, CA3 interneurons, and in CA1 pyramidal cells (Muller et al 2005).…”

Section: Important Parameters To Characterize Ca 2þ Buffers Intracellmentioning

confidence: 97%

“…The concentration of PV is as high as 1.5 mM in the superfast swimbladder muscle of toadfish (Tikunov and Rome 2009) and approximately 1 mM in mouse fast-twitch muscle, while it is lower in other muscles and highly correlated with the speed of muscle relaxation (Heizmann et al 1982). Within different neuron subpopulations, PV is on average one order of magnitude lower (50 -150 mM): 80 mM in mouse (Schmidt et al 2003b) and 120 mM in rat (Hackney et al 2005) Purkinje cells; 150 mM in mouse cerebellar interneurons (Collin et al 2005), and 100 -300 mM in inner and outer hair cells from inner ear (Hackney et al 2005). The concentration of mammalian b PV called oncomodulin (OM) is particularly high in rat cochlear outer hair cells (2-3 mM) (Hackney et al 2005).…”

Section: Important Parameters To Characterize Ca 2þ Buffers Intracellmentioning

confidence: 97%

“…Within different neuron subpopulations, PV is on average one order of magnitude lower (50 -150 mM): 80 mM in mouse (Schmidt et al 2003b) and 120 mM in rat (Hackney et al 2005) Purkinje cells; 150 mM in mouse cerebellar interneurons (Collin et al 2005), and 100 -300 mM in inner and outer hair cells from inner ear (Hackney et al 2005). The concentration of mammalian b PV called oncomodulin (OM) is particularly high in rat cochlear outer hair cells (2-3 mM) (Hackney et al 2005). High concentrations of CR (1.2 mM) are also present in tall saccular hair cells of the frog (Edmonds et al 2000).…”

Section: Important Parameters To Characterize Ca 2þ Buffers Intracellmentioning

confidence: 99%

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Cytosolic Ca2+ Buffers

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The Concentrations of Calcium Buffering Proteins in Mammalian Cochlear Hair Cells

Cited by 189 publications

References 61 publications

Upregulated expression of oncomodulin, the beta isoform of parvalbumin, in perikarya and axons in the diencephalon of parvalbumin knockout mice

Upregulated expression of oncomodulin, the beta isoform of parvalbumin, in perikarya and axons in the diencephalon of parvalbumin knockout mice

Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells

Cytosolic Ca2+ Buffers

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