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PubMed1998

AMPA receptor subunits are differentially expressed in parvalbumin- and calretinin-positive neurons of the rat hippocampus.

Recent studies suggest a functional diversity of native alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptor channels (AMPARs). In several types of interneurons, AMPARs are characterized by higher Ca2+ permeability and faster kinetics than AMPARs in principal cells. We studied the expression profile of AMPAR subunits in the hippocampal parvalbumin (PV)- and calretinin (CR)-positive cells, which represent different populations of non-principal cells. To this end, non-radioactive in situ hybridization with AMPAR subunit specific cRNAs was combined with immunocytochemistry for PV or CR. Double-immunolabelling using antibodies against AMPAR subunits and PV or CR was also performed. PV-containing neurons represent a fairly homogeneous population of cells expressing high levels of GluR-A and GluR-D mRNAs, moderate levels of GluR-C and low levels of GluR-B mRNAs in all the examined regions of hippocampus. The vast majority of CR-containing cells have a much lower expression of GluR-A, -C and -D mRNA than PV-positive neurons, although similarly featuring low levels of GluR-B mRNA. Only a subpopulation of CR-containing cells, the spiny neurons of the dentate gyrus and CA3 region of the hippocampus were characterized by a strong expression of GluR-A and -D subunit mRNAs. The differential pattern found for the AMPAR subunit mRNA expression was confirmed by immunocytochemistry at protein level. Despite the common feature of low GluR-B subunit expression, PV- and CR-containing interneurons differ with respect to the density and combination of their expressed AMPAR subunits. The different combination of subunits might subserve different properties of the AMPA channels featured by these cell types, with implications for the functioning of the hippocampal network.

Animals↗
PubMed2000

Alterations in Purkinje cell spines of calbindin D-28 k and parvalbumin knock-out mice.

The second messenger Ca2+ is known to act in a broad spectrum of fundamental cell processes, including modifications of cell shape and motility, through the intermediary of intracellular calcium-binding proteins. The possible impact of the lack of the intracellular soluble Ca2+-binding proteins parvalbumin (PV) and calbindin D-28 k (CB) was tested on spine morphology and topology in Purkinje cell dendrites of genetically modified mice. Three different genotypes were studied, i.e. PV or CB single knock-out (PV-/-, CB-/-) and PV and CB double knock-out mice (PV-/-CB-/-). Purkinje cells were microinjected with Lucifer Yellow and terminal dendrites scanned at high resolution with a confocal laser microscope followed by three-dimensional (3-D) reconstruction. The absence of PV had no significant effect on spine morphology, whereas the absence of CB resulted in a slight increase of various spine parameters, most notably spine length. In double knock-out mice, the absence of both PV and CB entailed a doubling of spine length, an increase in spine volume and spine surface, a higher spine density along the dendrites, as well as a more clustered spine distribution. In all three genotypes, a reduction in the number of stubby spines was observed compared with wild-type animals. These results suggest a morphological compensation for the lack of the soluble calcium buffers in the cytoplasm of Purkinje cell dendritic spines. The increase in various spine parameters, particularly volume, may counteract the lack of the calcium buffers, such as to adjust Ca2+-transients at the transitional zone between spines and dendrites.

Animals↗
PubMed2001

Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons.

The development of spontaneous limbic seizures was investigated in a rat model in which electrical tetanic stimulation of the angular bundle was applied for up to 90 min. This stimulation produced behavioural and electrographic seizures that led to a status epilepticus (SE) in most rats (71%). Long-term EEG monitoring showed that the majority of the rats (67%) that underwent SE, displayed a progressive increase of seizure activity once the first seizure was recorded after a latent period of about 1 week. The other SE rats (33%) did not show this progression of seizure activity. We investigated whether these different patterns of evolution of spontaneous seizures could be related to differences in cellular or structural changes in the hippocampus. This was the case regarding the following changes. (i) Cell loss in the hilar region: in progressive SE rats this was extensive and bilateral whereas in nonprogressive SE rats it was mainly unilateral. (ii) Parvalbumin and somatostatin-immunoreactive neurons: in the hilar region these were almost completely eliminated in progressive SE rats but were still largely present unilaterally in nonprogressive SE rats. (iii) Mossy fibre sprouting: in progressive SE rats, extensive mossy fibre sprouting was prominent in the inner molecular layer. In nonprogressive SE rats, mossy fibre sprouting was also present but less prominent than in progressive SE rats. Although mossy fibre sprouting has been proposed to be a prerequisite for chronic seizure activity in experimental temporal lobe epilepsy, the extent of hilar cell death also appears to be an important factor that differentiates between whether or not seizure progression will occur.

Animals↗
PubMed1995

Distribution of calretinin, calbindin D28k, and parvalbumin in subcellular fractions of rat cerebellum: effects of calcium.

The distribution of calretinin, calbindin D28k, and parvalbumin was examined in subcellular fractions prepared from rat cerebellum and analyzed by immunoblot. Calretinin was also quantified by radioimmunoassay. As expected, all three soluble, EF-hand calcium-binding proteins were predominantly localized in the cytosolic fraction. Calretinin and calbindin D28k were also detected in membrane fractions. Calretinin was more abundant in synaptic membrane than in microsomal fractions. The cerebellar microsomal fraction contained the greatest concentration of membrane-associated calbindin D28k. The association of calretinin and calbindin D28k with membrane fractions was decreased in samples prepared or incubated in low calcium. Quantification of calretinin in subcellular fractions of rat cerebellum revealed a greater amount of calretinin in cytosolic fractions prepared or incubated in low calcium and reduced amounts of calretinin in all membrane fractions incubated in low calcium with the exception of the mitochondrial fraction. These results imply that calretinin and calbindin D28k might have physiological target molecules that are associated with, or are components of, brain membranes.

Animals↗
PubMed2002

Electrical and chemical synapses among parvalbumin fast-spiking GABAergic interneurons in adult mouse neocortex.

Networks of gamma-aminobutyric acid (GABA)ergic interneurons connected via electrical and chemical synapses are thought to play an important role in detecting and promoting synchronous activity in the cerebral cortex. Although the properties of electrical and chemical synaptic interactions among inhibitory interneurons are critical for their function as a network, they have only been studied systematically in juvenile animals. Here, we have used transgenic mice expressing the enhanced green fluorescent protein in cells containing parvalbumin (PV) to study the synaptic connectivity among fast-spiking (FS) cells in slices from adult animals (2-7 months old). We have recorded from pairs of PV-FS cells and found that the majority of them were electrically coupled (61%, 14 of 23 pairs). In addition, 78% of the pairs were connected via GABAergic chemical synapses, often reciprocally. The average coupling coefficient for step injections was 1.5% (n = 14), a smaller value than that reported in juvenile animals. GABA-mediated inhibitory postsynaptic currents and potentials decayed with exponential time constants of 2.6 and 5.9 ms, respectively, and exhibited paired-pulse depression (50-ms interval). The inhibitory synaptic responses in the adult were faster than those observed in young animals. Our results indicate that PV-FS cells are highly interconnected in the adult cerebral cortex by both electrical and chemical synapses, establishing networks that can have important implications for coordinating activity in cortical circuits.

Action Potentials↗
PubMed1985

The Ca2+-binding protein parvalbumin: molecular cloning and developmental regulation of mRNA abundance.

Parvalbumin (PV) is a Ca2+-binding protein found only in vertebrates. It is postulated to serve as a soluble relaxing factor in fast mammalian muscle. We have isolated a rat PV cDNA clone and used this as a probe to examine changes in PV mRNA during muscle and brain development. A cDNA library was constructed in PUC8/PUC9 plasmid vectors from adult poly(A)+ RNA isolated from rat gastrocnemius muscle. The library was screened with a 17-mer oligonucleotide encoding amino acids 28-33 of rat PV. One recombinant (9f) was confirmed as a PV clone by DNA sequencing and was shown to contain 73% of the protein coding sequence. Hybridization of clone 9f to RNA separated by electrophoresis revealed two species 700 and 1100 nucleotides long but genomic blotting indicates that PV may be a single copy gene. Highest levels of PV mRNA are found in the gastrocnemius, which is a fast contracting/relaxing muscle. Skin contains the next highest amount of PV mRNA followed, in order, by brain and the slow twitch soleus muscle. Rat muscle PV mRNA levels increase 15- to 20-fold between postnatal days 4 and 20 as measured by dot blot hybridization of total RNA, whereas only a slight increase was observed when young and adult brains were compared. The changes in PV mRNA during development appear to be selective, because mRNA coding for the structurally homologous Ca2+-binding protein calmodulin (CaM) was found to change only slightly in muscle. However, CaM mRNA levels decrease during the early days of brain ontogeny. Thus, the mRNAs that encode the homologous Ca2+-binding proteins PV and CaM appear to be developmentally regulated in a tissue-specific manner.

Age Factors↗
PubMed1993

Immunocytochemical localization of the plasma membrane calcium pump, calbindin-D28k, and parvalbumin in Purkinje cells of avian and mammalian cerebellum.

A monoclonal antibody produced against the human erythrocyte plasma membrane calcium pump (PMCA) was shown to react immunohistochemically with an epitope of the PMCA in avian and mammalian cerebellum. Western blot analysis of purified synaptosomes and homogenates from avian cerebellum revealed major immunoreactive proteins with molecular masses (130 kDa and 138 kDa) similar to those of purified erythrocyte PMCA. Dual-imaging confocal immunofluorescence microscopy of avian cerebellum showed that the PMCA antibody stained the periphery of the soma whereas calbindin-D28k was located in the cytosol. PMCA heavily stained the more distal dendrites of the Purkinje cells and, within the resolution of the fluorescence procedure, colocalized with calbindin-D28k. By using alkaline phosphatase-conjugated second antibody, PMCA was again localized to the peripheral soma, to a segmental pattern in dendrites, and to presumed spiny elements. The soma periphery and dendrites of Purkinje cells of the rat cerebellum were also prominently stained with anti-PMCA antibody and compared to parvalbumin localization. Dendritic depolarization and dendritic spiking behavior are significant Ca(2+)-dependent events of Purkinje cells. The rapid decline of intracellular free Ca2+ after the rapid rise time of Ca2+ transients is considered to be due to sequestration by Ca2+ buffers, uptake by intracellular stores, and Ca2+ extrusion mechanisms, the latter a function of PMCA now shown immunohistochemically to be a prominent feature of Purkinje cell dendrites.

Alkaline Phosphatase↗
PubMed1995

Increase of skeletal muscle relaxation speed by direct injection of parvalbumin cDNA.

Parvalbumin (PV) is a high affinity Ca(2+)-binding protein found at high concentration in fast-contracting/relaxing skeletal muscle fibers of vertebrates. It has been proposed that PV acts in the process of muscle relaxation by facilitating Ca2+ transport from the myofibrils to the sarcoplasmic reticulum. However, on the basis of metal-binding kinetics of PV in vitro, this hypothesis has been challenged. To investigate the function of PV in skeletal muscle fibers, direct gene transfer was applied in normal and regenerating rat soleus muscles which do not synthesize detectable amounts of PV. Two weeks after in vivo transfection with PV cDNA, considerable levels of PV mRNA and protein were detected in normal muscle, and even higher amounts were detected in regenerating muscle. Twitch half-relaxation time was significantly shortened in a dose-dependent way in transfected muscles, while contraction time remained unaltered. The observed shortening of half-relaxation time is due to PV and its ability to bind Ca2+, because a mutant protein lacking Ca(2+)-binding capacity did not promote any change in physiology. These results directly demonstrate the physiological function of PV as a relaxing factor in mammalian skeletal muscle.

Animals↗
PubMed1998

Parvalbumin distribution in the musculature of the pharyngo-oesophageal segment.

The composition and size of muscle fibre types in the hyopharyngeus (HP), thyropharyngeus (TP), cricopharyngeus (CP) and cervical oesophageal muscle (CE) from 6 normal adult cats were investigated using parvalbumin (PA) immunohistochemistry. Fibre types I, IIA and IIB were identified in all muscles. HP and TP revealed predominance of type II fibres (74.8% and 75.2%, respectively), whilst CP and CE showed predominance of type I fibres (72.6% and 82.2%, respectively). The mean diameter of narrow fibres was greater in type II (23.9 microm) than in type I fibres (21.7 microm). The results seem to reflect the physiological features of each muscle, i.e. short rapid contractions of HP and TP, sustained contraction of CP and slow peristaltic movements of CE.

Animals↗
PubMed1995

Distribution of parvalbumin in specific fibre types of chicken skeletal muscles.

1. The distribution of parvalbumin (PA), which functions as a relaxing factor in the skeletal muscles, was examined in slow anterior latissimus dorsi (ALD), fast posterior latissimus dorsi (PLD), mixed sartorius (SA), pectoralis superficialis (PS) and pectoralis profundus (PP) muscles from chickens. 2. The biochemical characteristics of these muscles were confirmed by the assay of total lactate dehydrogenase (LDH) activity as well as the LDH isozymes for anaerobic metabolism, and by the photometrical analysis of myoglobin for anaerobic metabolism, and by the photometrical analysis of myoglobin for aerobic metabolism. 3. PA in individual muscles was determined by a sandwich ELISA and was demonstrated by 2-dimensional polyacrylamide-gel electrophoresis. 4. Because of poor myoglobin and higher LDH activity or M-type isozyme pattern, the PLD was confirmed as containing primarily fast-twitch glycolytic and oxidative-glycolytic (FG/FOG) fibres, while the SA was shown to be composed mostly of FOG fibres because of the highest myoglobin content and the intermediate LDH activity or H and M-type isozyme pattern. PA content was high and variable in both PLD and SA. 5. PA was undetectable in the ALD which appears to contain exclusively slow-tonic (ST) fibres, being verified by its myoglobin-rich nature and lowest LDH activity or predominant H-type isozyme characteristics. PA was absent from the PS ad PP, which probably contain predominantly FG fibres because of negligible amounts of myoglobin and the highest LDH activities or M-type isozyme pattern.

Animals↗
PubMed2002

'New' functions for 'old' proteins: the role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice.

Calretinin (CR), calbindin D-28k (CB) and parvalbumin (PV) belong to the large family of EF-hand calcium-binding proteins, which comprises more than 200 members in man. Structurally these proteins are characterized by the presence of a variable number of evolutionary well-conserved helix-loop-helix motives, which bind Ca2+ ions with high affinity. Functionally, they fall into two groups: by interaction with target proteins, calcium sensors translate calcium concentrations into signaling cascades, whereas calcium buffers are thought to modify the spatiotemporal aspects of calcium transients. Although CR, CB and PV are currently being considered calcium buffers, this may change as we learn more about their biology. Remarkable differences in their biophysical properties have led to the distinction of fast and slow buffers and suggested functional specificity of individual calcium buffers. Evaluation of the physiological roles of CR, CB and PV has been facilitated by the recent generation of mouse strains deficient in these proteins. Here, we review the biology of these calcium-binding proteins with distinct reference to the cerebellum, since they are particularly enriched in specific cerebellar neurons. CR is principally expressed in granule cells and their parallel fibres, while PV and CB are present throughout the axon, soma, dendrites and spines of Purkinje cells. PV is additionally found in a subpopulation of inhibitory interneurons, the stellate and basket cells. Studies on deficient mice together with in vitro work and their unique cell type-specific distribution in the cerebellum suggest that these calcium-binding proteins have evolved as functionally distinct, physiologically relevant modulators of intracellular calcium transients. Analysis of different brain regions suggests that these proteins are involved in regulating calcium pools critical for synaptic plasticity. Surprisingly, a major role of any of these three calcium-binding proteins as an endogenous neuroprotectant is not generally supported.

Animals↗
PubMedDate not supplied

Selective changes in the microorganization of the human epileptogenic neocortex revealed by parvalbumin immunoreactivity.

The microanatomy of the human lateral temporal cortex removed from patients with intractable temporal lobe epilepsy was studied using correlative light and electron microscopic immunocytochemical methods for the localization of the calcium-binding protein parvalbumin (PV). PV immunostaining was mainly used to label a subpopulation of powerful cortical inhibitory interneurons that have been shown to be lost at epileptic foci in certain animal models of epilepsy. In the human neocortex with normal appearance, we identified the same local neuronal circuitry as in the normal monkey cortex, but in some regions of the same cortex, a fine disorganization of neuronal circuits (loss of inhibitory neurons and presumptive thalamocortical terminals) was found. This abnormal circuitry may interfere with normal cerebral activity in epileptic patients. These results also indicate that PV immunoreactivity can be a useful tool to study normal and abnormal synaptic circuits in the human cerebral cortex.

Adolescent↗
PubMedDate not supplied

Prenatal development of parvalbumin immunoreactivity in the human striate cortex.

In human primary visual cortex, parvalbumin (PV) is expressed by Cajal-Retzius cells in layer I by 20 weeks of gestation (20W), but its immunoreactivity is mostly lost by term. PV immunoreactivity in layers II-VI mainly develops later, from 26 to 34W, following an approximately 'inside-outside' sequence in a series of bands. PR-positive perikarya appear in layer V by 20W, but only in small numbers. They increase in number and staining intensity by 26W. By 30W a band of densely labelled somata and neuropil occupies layers IVC-VI. By 34W a second, less dense, band of cell bodies and neuropil appears in IVB and IVCalpha, separated from the deep band by IVCbeta which is cell-sparse and almost fibre-free. Between 38 and 40W, a third minor band consisting mainly of fibres is seen in layer IVA. Reactive cell bodies form clusters, and the neuropil staining is mosaic-like. PV-positive neurons are of two main types: large with wide dendritic arbor, and smaller with simpler dendrites. However, a few have characteristics of pyramidal cells, and a few others resemble glial cells. The laminar pattern of PV-immunoreactive somata in human striate cortex is established by term, rather than postnatally as in most mammals, implying that PV may be involved in neuronal development in prenatal human striate cortex.

Female↗
PubMedDate not supplied

Dopamine innervation of a subclass of local circuit neurons in monkey prefrontal cortex: ultrastructural analysis of tyrosine hydroxylase and parvalbumin immunoreactive structures.

The ability of dopamine to regulate the cognitive functions of the prefrontal cortex (PFC) involves complex modulatory actions on GABA-containing local circuit neurons in addition to pyramidal cells. However, the subclasses of cortical neurons that receive direct dopamine input are not known. We sought to determine whether dopamine terminals innervate the subclasses of local circuit neurons that contain the calcium-binding protein parvalbumin (PV), namely the wide arbor and chandelier neurons that target pyramidal cell soma and axon initial segments respectively. Sections through area 9 of five monkeys were labeled with immunoperoxidase for tyrosine hydroxylase (TH), to identify dopamine terminals, and with immunogold-silver for PV. Electron microscopic examination of the middle cortical layers (IIIb-IV) revealed that TH-positive terminals were sometimes directly apposed to PV-labeled dendrites, and approximately one-third of these contacts exhibited morphological features that are typically associated with symmetric synapses. In contrast, TH-immunolabeled terminals in the superficial layers (I-IIIa) were less frequently apposed to PV-positive dendrites, and none of these contacts exhibited synapse-like morphology. These findings, in concert with previous studies of GABA- or calretinin-containing local circuit neurons, suggest that dopamine's modulatory action in the PFC involves selective effects on only certain interneuron populations, including those that mediate potent inhibitory actions on pyramidal cells.

Animals↗
PubMedDate not supplied

Postnatal development of calcium-binding proteins calbindin and parvalbumin in human visual cortex.

In adult primate visual cortex, the calcium-binding proteins calbindin (CB) and parvalbumin (PV) are localized in different subsets of GABAergic neurons with a characteristic laminar distribution. However, the emergence and development of CB and PV in relation to the periods of functional maturation of the human visual cortex are not known. Therefore, we examined (i) postnatal changes in the distribution of immunoreactivity (ir) for CB and PV in the visual cortex; (ii) the pattern of changes in immunoreactivity in relation to the synaptic maturation; and (iii) differences in the maturation of CB and PV immunoreactivity between areas 17 and 18. We found a consistently high expression of CB in neonatal visual cortex, particularly in layer IV and infragranular layers. However, despite an early appearance of PV, its peak in development occurred only after 2 months of age, characterized by a transient overexpression in the thalamo-recipient layer IV and a continuous inside-out maturation in supragranular layers. The neonatal pattern of high CB-ir in layers IV-VI was transformed during infancy and childhood into an adult pattern of high CB-ir in layer II, but low CB-ir in layer IV and infragranular layers. There was no difference in pattern and tempo of maturation of calcium-binding proteins between area 17 and 18, indicating simultaneous development of cortical inhibitory circuits among cytoarchitectonically and functionally distinct cortical areas. In addition, the reorganization of CB/PV expression temporally and spatially coincides with the course of cortical synaptogenesis, and delineates the major stages of maturation of the human visual cortex.

Adolescent↗
PubMed2004

Parvalbumin expression in visual cortical interneurons depends on neuronal activity and TrkB ligands during an Early period of postnatal development.

The differentiation of cortical interneurons is controlled by environmental factors. Here, we describe the role of activity and neurotrophins in regulating parvalbumin (PARV) expression using organotypic cultures (OTC) of rat visual cortex as model system. In OTC, PARV expression was dramatically delayed. The organotypic proportion of approximately 6% PARV neurons was not established before 50-70 DIV, whereas in vivo all neurons are present until P20. Thalamic afferents increased cortical PARV mRNA in OTC, but not to the age-matched in vivo level. During the first 10 DIV, BDNF and NT-4 accelerated PARV mRNA expression in a Trk receptor and MEK2 dependent manner. The BDNF action required PI3 kinase signalling. PARV expression required activity. The proportion of neurons which managed to up-regulate PARV was inversely related to the duration of early transient periods of activity deprivation. Long-term activity-deprived OTC completely failed to up-regulate PARV mRNA. Both TrkB ligands failed to promote PARV expression in activity-deprived OTC. However, a few basket and chandelier neurons were observed, suggesting that the development of class-specific morphological features is activity-independent. Once established, PARV expression became resistant to late-onset activity deprivation. In conclusion, PARV expression depended on activity and TrkB ligands which appear to prime the PARV expression already before its developmental onset.

Afferent Pathways↗
PubMed2004

Increases in the density of parvalbumin-immunoreactive neurons in anterior cingulate cortex of amphetamine-withdrawn rats: evidence for corticotropin-releasing factor in sustained elevation.

We previously reported synchronization of pyramidal neurons within prefrontal cortex of rats repeatedly exposed to amphetamine (AMPH). To test the hypothesis that cortical synchronization may be related to changes in local GABA signaling, we used antibodies specific for parvalbumin (PV), calbindin D28k (CB) and calretinin (CR) as selective labels for three distinct GABA interneuron classes in the anterior cingulate cortex (ACC) of similarly treated rats. We observed a selective increase in the density of PV-immunoreactive (ir), but not CB-ir or CR-ir, neurons in the ACC of AMPH-treated rats at both 1 day and 7 day withdrawal. Increased density of PV-ir GABA interneurons in the ACC at 1 day withdrawal was reproduced in rats repeatedly injected with apomorphine or with SKF-38393. Thus, the critical role of DA receptors during AMPH exposure is evident. However, DA receptor activation did not appear to account for the PV up-regulation in AMPH-treated rats at 7 day withdrawal. Significantly higher numbers of pericellular basket-like puncta immunoreactive for corticotropin-releasing factor (CRF) were observed in the ACC of AMPH rats at 7 day withdrawal. Combined dual immunofluorescence and confocal microscopy further revealed that CRF-ir puncta made possible pericellular contacts on PV-ir (not CB-, CR- or glutamate-ir) cell bodies. A potential cellular mechanism seems to emerge that CRF-ir terminals, that may be underdetected under normal conditions due to low activity levels, may be functionally activated during psychostimulant withdrawal, thereby altering local GABAergic signaling.

Amphetamine↗
PubMed1987

Ca2+- and Sr2+-sensitivity of the ATPase activity of rabbit skeletal myofibrils: effect of the complete substitution of troponin C with cardiac troponin C, calmodulin, and parvalbumins.

The Ca2+-sensitive ATPase activity of rabbit skeletal myofibrils disappeared completely after treatment with a solution containing CDTA, a strong divalent cation chelator, at a low ionic strength. A gel electrophoretic study revealed that all troponin C and about half of myosin light chain 2 were removed from the myofibrils by the CDTA treatment. The CDTA-treated myofibrils, when reconstituted with skeletal troponin C, showed almost exactly the same Ca2+- or Sr2+-sensitive ATPase activity as that of intact myofibrils. The CDTA-treated myofibrils reconstituted with porcine cardiac troponin C showed the same Ca2+- or Sr2+-sensitivity of the ATPase as that of porcine cardiac myofibrils; Sr2+-sensitivity relative to Ca2+-sensitivity was about ten times higher than, and the maximal slope of the activation curve was about half that of skeletal myofibrils. These findings indicate that these characteristic features of divalent cation regulation in the contraction of skeletal and cardiac muscles are determined solely by the species of troponin C. Bovine brain calmodulin hardly activated the ATPase activity of the CDTA-treated myofibrils even in the presence of Ca2+. Excess calmodulin, however, was found to give Ca2+- or Sr2+-sensitivity to the ATPase activity of the CDTA-treated myofibrils. Frog skeletal parvalbumins 1 and 2, even in excess, did not affect the ATPase activity of the CDTA-treated myofibrils.

Adenosine Triphosphatases↗