Biomedical subjects

J Knapp

Publications and source records attributed to J Knapp.

At least 19 recordsLinked to original sources

PubMed2006

Taxonomic position and geographical distribution of the common sheep G1 and camel G6 strains of Echinococcus granulosus in three African countries.

The taxonomic and phylogenetic status of Echinococcus granulosus strains are still controversial and under discussion. In the present study, we investigated the genetic polymorphism of E. granulosus isolates originating from three countries of Africa, including a region of Algeria, where the common G1 sheep and the camel G6 strains coexist sympatrically. Seventy-one hydatid cysts were collected from sheep, cattle, camels, and humans. Two mitochondrial markers (cox1 and nad1) were used for strain identification. Two nuclear markers (actII and hbx2) were used to study the possible occurrence of cross-fertilization. Despite the heterogeneity observed among the G1 isolates, they were all localized within one robust cluster. A second strong cluster was also observed containing all of the G6 isolates. Both strains appeared as two distinct groups, and no cases of interbreeding were found. Thus, the attribution of a species rank can be suggested. We also found the Tasmanian sheep G2 strain for the first time in Africa. Because of the slight variations observed between the common sheep and the Tasmanian sheep strains, further studies should be carried out to elucidate the epidemiological relevance of this genetic discrimination.

Algeria↗

PubMed2006

EmsB, a tandem repeated multi-loci microsatellite, new tool to investigate the genetic diversity of Echinococcus multilocularis.

In order to explore the genetic diversity within Echinococcus multilocularis (E. multilocularis), the cestode responsible for the alveolar echinococcosis (AE) in humans, a microsatellite, composed of (CA) and (GA) repeats and designated EmsB, was isolated and characterized in view of its nature and potential field application. PCR-amplification with specific primers exhibited a high degree of size polymorphism between E. multilocularis and Echinococcus granulosus sheep (G1) and camel (G6) strains. Fluorescent-PCR was subsequently performed on a panel of E. multilocularis isolates to assess intra-species polymorphism level. EmsB provided a multi-peak profile, characterized by tandemly repeated microsatellite sequences in the E. multilocularis genome. This "repetition of repeats" feature provided to EmsB a high discriminatory power in that eight clusters, supported by bootstrap p-values larger than 95%, could be defined among the tested E. multilocularis samples. We were able to differentiate not only the Alaskan from the European samples, but also to detect different European isolate clusters. In total, 25 genotypes were defined within 37 E. multilocularis samples. Despite its complexity, this tandem repeated multi-loci microsatellite possesses the three important features for a molecular marker, i.e. sensitivity, repetitiveness and discriminatory power. It will permit assessing the genetic polymorphism of E. multilocularis and to investigate its spatial distribution in detail.

Animals↗

PubMed2005

Genetic typing of Echinococcus granulosus in Romania.

In Romania, cystic echinococcosis is endemic and affects, besides humans, various animal species including sheep, cattle, and swine. As yet, no molecular-genetic typing has been carried out to clearly identify the putative strains being transmitted there. Parasite samples (protoscoleces or germinal layers) were collected from infected intermediate hosts and subsequently analyzed by comparing the PCR-amplified DNA sequences of three targets: one nuclear (BG1/3) and two mitochondrial (cox1 and nadI). Three strains were identified with the mitochondrial sequences: (i) the common sheep strain (G1) which circulates between sheep and cattle and is infective for humans, (ii) the Tasmanian sheep strain (G2) infecting sheep and cattle, and (iii) the pig strain (G7) predominantly found in swine. To our knowledge, this is the first report which demonstrates the occurrence of the Tasmanian sheep strain in cattle and the sympatric occurrence of these three strains (G1, G2, and G7) in Europe.

Animals↗

PubMed2005

Surface contact measurement of electrical cell uncoupling in the mouse heart during ischemia.

Electrical cell uncoupling via gap junction closure is assumed to cause characteristic changes of the passive dielectric spectrum of ischemic heart tissue. In order to find an independent evidence for this assumption, we analysed heart tissue during ischemia, measured the open state of gap junctions by means of dye transfer and correlated this parameter with the time course of the dielectric permittivity. The hearts were pre-ischemically arrested by perfusion with Ringer solution containing 20 mmol/L of potassium (group KCL, n=10). This solution was also used with the addition of two gap junction blockers, either 3 mmol/L heptanol (group HEP, n=4) or 20 micromol/L palmitoleic acid (group PA, n=7). During subsequent ischemia at 21.0+/-0.5 degrees C, we monitored the passive dielectric permittivity spectrum and the spread of dye. After a sigmoidal increase the dielectric permittivity reached an upper plateau at 61+/-22 min of ischemia in KCL, at 45+/-7 min in PA, and already during perfusion at 2+/-1 min in group HEP. At the beginning of ischemia, dye migrated to neighbouring cells in groups KCL and PA but not in HEP. In KCL and PA, the intercellular diffusion of dye stopped after 64+/-26 and 40+/-11 min of ischemia, respectively. Our results suggest that the sigmoidal increase in dielectric permittivity and the reduction of dye diffusion depend on a common mechanism, namely gap junction closure.

Animals↗

PubMed2001

Enhanced protein phosphorylation in hypertensive hypertrophy.

OBJECTIVE: Chronic pressure overload in spontaneously hypertensive rats (SHR) is accompanied by heart hypertrophy and signs of heart failure. Since there is growing evidence for a possible pathophysiological role of altered protein phosphorylation in heart hypertrophy and failure, we studied here cardiac regulatory phosphoproteins and the kinases and phosphatases which regulate their phosphorylation state. METHODS: The experiments were performed in ventricles of SHR (12-13 weeks old) and age-matched normotensive Wistar-Kyoto rats (WKY). RESULTS: Basal as well as isoproterenol (Iso)-stimulated force of contraction (FOC) was markedly decreased in isolated electrically driven papillary muscles of SHR. Iso (3 micromol/l, 10 min) increased FOC by 0.91+/-0.20 mN in SHR and by 3.88+/-0.52 mN in WKY, respectively. Ca(2+)-uptake by sarcoplasmic reticulum (SR) at low ionized Ca(2+)-concentration was increased in homogenates from SHR. This was not due to altered expression of phospholamban (PLB), SR-Ca(2+)-ATPase and calsequestrin. However, PLB-phosphorylation at threonine-17 (PLB-PT-17) and the activity of Ca(2+)/calmodulin dependent protein kinase (Ca(2+)/Cam-PK) was increased in SHR. In addition, we found an enhanced protein kinase A (PKA)-dependent phosphorylation of the inhibitory subunit of troponin (TnI). In contrast, there was no difference in the activity or expression (protein- and mRNA-level) of protein phosphatases type 1 or type 2A between SHR and WKY. CONCLUSIONS: It is suggested that increased Ca(2+)/Cam-PK-activity with resulting increase of PLB-PT-17 enhanced SR-Ca(2+)-uptake in SHR and might contribute to the pathophysiological changes in cardiac hypertrophy of SHR.

Adrenergic beta-Agonists↗

PubMed2001

Activation and inactivation of cAMP-response element-mediated gene transcription in cardiac myocytes.

OBJECTIVE: Chronic beta-adrenergic stimulation of the cAMP-dependent signalling pathway is implicated in functionally relevant expressional changes in congestive heart failure. We studied activation and inactivation of the cardiac gene transcription mediated by the cAMP-response element (CRE) and the CRE-binding protein (CREB) as an important mechanism of a cAMP-dependent gene regulation. METHODS: We investigated the transcriptional activation by forskolin, an activator of the adenylyl cyclase, in chick embryonic cardiomyocytes transfected with a CRE-controlled luciferase construct in comparison to the phosphorylation and expression of CREB determined on immunoblots. RESULTS: Forskolin (10 micromol/l; 8 h) increased CRE-mediated transcription and phosphorylation of CREB 13- and 1.5-fold, respectively. The phosphorylation was further elevated in combination with cantharidin, an inhibitor of type 1+2A protein phosphatases. The transcriptional response to forskolin was desensitized by pretreatment with forskolin (1 micromol/l; 24 h) while CREB phosphorylation was increased. In forskolin-pretreated cells, total CREB protein levels were decreased. Cantharidin did not restore the attenuated transcriptional response. CONCLUSIONS: In cardiomyocytes, there is an activation of the CRE-mediated gene transcription by forskolin that is attenuated after prolonged stimulation, and this attenuation is not dependent from a dephosphorylation of CREB. We suggest that attenuation of the CRE-mediated transcription through chronic stimulation of the cAMP-pathway, e.g. by elevated catecholamines, contributes to the altered expressional regulation in congestive heart failure.

1-Methyl-3-isobutylxanthine↗

PubMed2001

Functional properties of the rat phosphatase 1alpha promoter.

The aim of this study was to investigate the functional properties of the promoter of the protein phosphatase 1alpha catalytic subunit. Luciferase plasmids with different fragments of the rat catalytic subunit of the protein phosphatase 1alpha promoter ranging from -3.7 kbp to -59 bp were transiently transfected into cells by the calcium-phosphate precipitation method. The promoter activity was determined in the absence and presence of inotropic agents which influencing the cAMP-depending pathway. The basal transcriptional activity decreased at fragment -124 bp and shorter fragments. To identify regions of regulatory importance we investigated the cAMP-dependent influence on the transcriptional activity. Stimulation of the complete promoter region with forskolin (1-100 microM) for 6 h led to a concentration-dependent decrease of transcriptional activity. Moreover, regions shorter than 3.7 kbp were inhibited by forskolin (10 microM). Short time stimulation (10 min) with forskolin (10 microM) increased the transcriptional activity of only the 3.7 kbp fragment. The effects were antagonized by Rp-cAMPS, a specific antagonist of protein kinase A, indicating cAMP-dependent effects. The results provide evidence for cAMP-dependent regulation of the protein phosphatase 1alpha promotor.

Animals↗

PubMed2001

Role of protein phosphatases in regulation of cardiac inotropy and relaxation.

We studied the effects of the protein phosphatase (PP) inhibitor cantharidin (Cant) on time parameters and force of contraction (FOC) in isometrically contracting electrically driven guinea pig papillary muscles. We correlated the mechanical parameters of contractility with phosphorylation of the inhibitory subunit of troponin (TnI-P) and with the site-specific phosphorylation of phospholamban (PLB) at serine-16 (PLB-Ser-16) and threonine-17 (PLB-Thr-17). Cant (after 30 min) started to increase FOC (112 +/- 4% of control, n = 10) and TnI-P and PLB-Thr-17 (120 +/- 5 and 128 +/- 7% of control) without any alteration of relaxation time. Cant (10 microM) started to increase PLB-Ser-16, but the relaxation was shortened at only 100 microM (from 140 +/- 9 to 116 +/- 12 ms, n = 9). Moreover, 100 microM Cant, 3 min after application, started to increase PLB-Thr-17, TnI-P, and FOC. Cant (100 microM) began to increase PLB-Ser-16 after 20 min. This was accompanied by shortening of relaxation time. Differences in protein kinase activation or different substrate specificities of PP may explain the difference in Cant-induced site-specific phosphorylation of PLB in isometrically contracting papillary muscles. Moreover, PLB-Thr-17 may be important for inotropy, whereas PLB-Ser-16 could be a major determinant of relaxation time.

Animals↗

PubMed2000

Lamprey hemoglobin. Structural basis of the bohr effect.

Lampreys, among the most primitive living vertebrates, have hemoglobins (Hbs) with self-association and ligand-binding properties very different from those that characterize the alpha(2)beta(2) tetrameric Hbs of higher vertebrates. Monomeric, ligated lamprey Hb self-associates to dimers and tetramers upon deoxygenation. Dissociation to monomers upon oxygenation accounts for the cooperative binding of O(2) and its pH dependence. Honzatko and Hendrickson (Honzatko, R. B., and Hendrickson, W. A. (1986) Proc. Natl. Acad. Sci. U. S. A 83, 8487-8491) proposed that the dimeric interface of the Hb resembles either the alpha(1)beta(2) interface of mammalian Hbs or the contacts in clam Hb where the E and F helices form the interface. Perutz (Perutz, M. F. (1989) Quart. Rev. Biophys. 2, 139- 236) proposed a version of the clam model in which the distal histidine swings out of the heme pocket upon deoxygenation to form a bond with a carboxyl group of a second monomer. The sedimentation behavior and oxygen equilibria of nine mutants of the major Hb component, PMII, from Petromyzon marinus have been measured to test these models. The results strongly support a critical role of the E helix and the AB corner in forming the subunit interface in the dimer and rule out the alpha(1)beta(2) model. The pH dependence of both the sedimentation equilibrium and the oxygen binding of the mutant E75Q indicate that Glu(75) is one of two groups responsible for the Bohr effect. Changing the distal histidine 73 to glutamine almost completely abolishes the self-association of the deoxy-Hb and causes a large increase in O(2) affinity. The recent x-ray crystallographic determination of the structure of deoxy lamprey Hb, reported after the completion of this work (Heaslet, H. A., and Royer, W. E. (1999) Structure 7, 517-526), shows that the dimer interface does involve the E helix and the AB corner, supporting the measurements and interpretations reported here.

Animals↗

PubMed2000

Regional expression of protein phosphatase type 1 and 2A catalytic subunit isoforms in the human heart.

In mammalian species, including man, the duration of myocardial contraction is shorter in atria than ventricles. Total contraction time depends at least in part on phosphorylation and dephosphorylation of cardiac regulatory proteins. Dephosphorylation reactions are mediated by protein phosphatases. In the mammalian heart more than 90% of the protein phosphatase (PP) activity consists of PP1 and PP2A. Therefore, the aim of this study was to investigate which isoforms of PP1 and PP2A are present in human myocardium and whether their expression is regionally different. RT-PCR and Northern blotting revealed that all isoforms of PP1 and PP2A presently known are expressed in the human heart. Expression levels of PP1 alpha, delta, and gamma as well as 2A alpha were higher in right ventricles than in right atria. However, there was no such difference for PP2A beta. At the protein level PP1 alpha was unchanged, whereas PP2A was by 56% higher in right ventricles compared to atria. The phosphorylation state of TnI was lower in right ventricle than in right atrium. Thus, lower protein expression of PP2A in atrium could contribute to the faster relaxation by increasing the phosphorylation state of TnI. We conclude that expression of PP1 and PP2A isoforms is regionally regulated in the human heart.

Blotting, Northern↗

PubMed2000

Protein phosphatase activity is increased in a rat model of long-term beta-adrenergic stimulation.

We tested the hypothesis that altered phosphorylation of Ca2+ regulatory proteins contributes to contractile anomalies in cardiac hypertrophy. Cardiac hypertrophy was induced in rats by chronic s.c. administration of isoproterenol (Iso, 2.4 mg/kg/day) via osmotic minipumps. On day 2 of Iso treatment the expression of atrial natriuretic factor was increased, time of relaxation in isolated papillary muscles shortened and protein expression of phospholamban (PLB) and sarcoplasmic reticulum Ca2+-ATPase reduced. In addition, the phosphorylation state of PLB at serine-16 and threonine-17 was decreased from (arbitrary units) 2.3+/-0.3 to 1.1+/-0.2 and from 4.1+/-0.6 to 2.1+/-0.2, respectively. This was not accompanied by altered activity of PLB-phosphorylating protein kinases (protein kinase A or Ca2+/calmodulin-dependent protein kinase II), whereas the activity of types 1 and 2A protein phosphatases (PP1 and -2A respectively) was enhanced from 1.1+/-0.08 to 1.71+/-0.13 nmol/mg/min. Iso treatment did not alter the PP1/PP2A activity ratio and 1 nmol/l okadaic acid, a concentration which completely blocks the catalytic subunit of PP2A, inhibited about 40% of total PP activity in all groups studied. These data indicate that the activity of both PP1 and PP2A were increased. All effects of Iso treatment were abolished by co-administration of propranolol (29.7 mg/kg/day). It is concluded that dephosphorylation of PLB is due to enhanced activity of PP1 and PP2A. We suggest that chronic beta-adrenergic stimulation, which occurs in human cardiac hypertrophy and failure, can lead to increased activity of PPs. This may contribute to altered contractile responses in the hypertrophied heart.

Adrenergic beta-Agonists↗

PubMed2000

The early response genes c-jun and HSP-70 are induced in regional cardiac stunning in conscious mammals.

OBJECTIVES: A reversible contractile dysfunction without necrosis after transient myocardial ischemia has been termed stunning. The molecular mechanisms underlying this phenomenon are only now beginning to be unraveled. It is conceivable that the expression of early-response genes may play a crucial role in stunning. METHODS: The expression of HSP-70, c-jun, and GRP-94 was investigated in a chronically instrumented dog model (n = 9). The left anterior descending coronary artery was occluded temporarily for 10 minutes after the animals had fully recovered from instrumentation. The wall thickening fraction was measured in the left anterior descending coronary artery and the nonischemic ramus circumflex of the left coronary artery-perfused region. When the wall thickening fraction of the left anterior descending coronary artery had recovered to 50% of preocclusion values, tissue samples were obtained from the areas perfused by the left anterior descending coronary artery and the nonischemic ramus circumflex of the left coronary artery. RESULTS: The messenger RNA of HSP-70 was increased to 214% +/- 26% in the area perfused by the left anterior descending artery compared with that perfused by the nonischemic ramus circumflex of the left coronary artery. There was no difference in the messenger RNA of GRP-94. The HSP-70 content was elevated to 130% +/- 14% in the left anterior descending artery compared with the area perfused by the ramus circumflex of the left coronary artery, and the c-jun protein content was 70% +/- 25% higher in the ischemic area compared with the control area. CONCLUSIONS: The induction of early-response genes observed here may indicate that they play an adaptive role in myocardial stunning, even in conscious mammals.

Animals↗

PubMed2000

Inhibitor potencies and substrate preference for endothelin-converting enzyme-1 are dramatically affected by pH.

Phosphoramidon has been shown to inhibit endothelin-converting enzyme-1 (ECE-1) in a remarkably pH-dependent manner (Ahn et al. Arch Biochem Biophys 1998;359:258-68). In order to determine whether this dramatic pH-dependence is a general phenomenon of ECE-1, two structurally unrelated ECE-1 inhibitors, PD 069185 and CGS 31447, were tested for ECE-1 inhibition at various pH values. Our data indicate that the potencies of these ECE-1 inhibitors are also highly affected by pH. ECE-1 is known to have a very sharp activity optimum at neutral pH which is in marked contrast to the acidic pH optimum for ECE-2. However, our results show that the pH optimum for ECE-1 activity is highly substrate-dependent. ECE-1 hydrolyzes the small peptide hormones bradykinin and substance P with acidic pH optima of 5.6-5.8, which sharply contrasts the neutral pH optimum with big ET-1 as substrate. These data suggest that the substrate preference for ECE-1 is highly affected by pH and that this pH-dependence for substrate preference might be one way of controlling the specificity of the enzyme in vivo.

Aspartic Acid Endopeptidases↗

PubMed2000

Biochemical mechanism(s) of stunning in conscious dogs.

The mechanism(s) underlying contractile dysfunction in cardiac stunning is not completely understood. The expression and/or the phosphorylation state of cardiac Ca(2+) homoeostasis-regulating proteins might be altered in stunning. We tested this hypothesis in a well-characterized model of stunning. Conscious dogs were chronically instrumented, and the left anterior descending artery (LAD) was occluded for 10 min. Thereafter, reperfusion of the LAD was initiated. Tissues from reperfused LAD (stunned) and Ramus circumflexus (control) areas were obtained when left ventricular regional wall thickening fraction had recovered by 50%. Northern and Western blotting revealed no differences in the expression of the following genes: phospholamban, calsequestrin, sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, and the inhibitory subunit of troponin I (TnI). However, the phosphorylation state of TnI and phospholamban were reduced in the LAD area. Fittingly, cAMP levels were reduced by 28% (P < 0.05). It is concluded that the contractile dysfunction in cardiac stunning might be mediated in part by decreased levels of cAMP and subsequently a reduced phosphorylation state of phospholamban and TnI.

Animals↗

PubMed2000

On the cardiac contractile, electrophysiological and biochemical effects of endothall, a protein phosphatase inhibitor.

Protein phosphatase inhibitors, e.g. cantharidin, exert positive inotropic effects in mammalian heart preparations. Endothall, a synthetic herbicide which is chemically related to cantharidin, inhibits protein phosphatase activities in mouse liver preparations. However, the cardiac effects of endothall have hitherto not been studied. In guinea pig papillary muscles, endothall (1-100 micromol/l) failed to affect force of contraction, whereas cantharidin (1-100 micromol/l) increased force of contraction maximally to 313.4 +/- 32% of control at 10 micromol/l. In isolated guinea pig ventricular cardiomyocytes, endothall did neither change the free intracellular calcium concentration nor the amplitude of calcium current nor the phosphorylation state of regulatory phosphoproteins like phospholamban. In contrast, cantharidin (30 micromol/l) increased the free intracellular calcium concentration and the L-type calcium current to 149.6 +/- 9% and to 157.6 +/- 12% of control, respectively. Furthermore, cantharidin (1-100 micromol/l) augmented the phosphorylation of phospholamban maximally to 140.8 +/- 7% of control. Nevertheless, in guinea pig ventricular homogenates, both endothall and cantharidin inhibited phosphatase activity with EC(50) values of 1.92 and 0.32 micromol/l, respectively. Thus, in contrast to cantharidin, endothall failed to increase force of contraction, though it inhibited protein phosphatase activity. Clearly, endothall is not an appropriate tool to study the function of protein phosphatases in the mammalian heart.

Animals↗

PubMed2000

Cantharidin enhances norepinephrine-induced vasoconstriction in an endothelium-dependent fashion.

In this study we characterized the effects of the protein phosphatase (PP) type 1 and type 2A inhibitor cantharidin (Cant) and its structural analogs cantharidic acid and endothall on PP activity, force of contraction, and myosin light chain phosphorylation in rat aorta. All compounds inhibited PP activity in homogenates of rat aorta with a rank order of potency of Cant = cantharidic acid > endothall. However, only Cant increased force of contraction and myosin light chain phosphorylation in intact isolated rat aortic rings. Based on these findings, we investigated the effects of Cant on alpha-adrenoceptor-mediated vasoconstriction. Cant (1 and 3 microM) enhanced norepinephrine-induced contraction in endothelium-intact rat aorta. In contrast, Cant did not affect norepinephrine-induced contraction in endothelium-denuded rat aorta. We suggest that inhibition of PP1 and/or PP2A activities by Cant enhances vascular contractility in endothelium-intact rat aorta by increasing the phosphorylation state of endothelial regulatory proteins.

Animals↗

PubMed2000

Functional properties of transgenic mouse hearts overexpressing both calsequestrin and the Na(+)-Ca(2+) exchanger.

Overexpression of calsequestrin (CSQ) induces severe cardiac hypertrophy, whereas overexpression of Na(+)-Ca(2+) exchanger (NCX) does not affect cardiac weight. To investigate a possible beneficial effect of NCX in hypertrophy, we produced transgenic mice overexpressing both NCX and CSQ (NCX/CSQ). Surprisingly, these mice developed severe heart failure. The heart/body weight ratio was enhanced and the mRNA expression of ANF, as a marker of hypertrophy, was highest in double transgenic mice. In isolated muscle strips, the basal relaxation time was prolonged in CSQ and NCX/CSQ mice. Moreover, in the presence of caffeine, force of contraction was increased only in CSQ and NCX/CSQ and was accompanied by elevated diastolic tension. In some respects, however, additional overexpression of NCX altered the CSQ phenotype into the wild-type phenotype. The expression of sarcoplasmic reticulum (SR)-Ca(2+)-ATPase and phospholamban, proteins involved in the Ca(2+) uptake of the SR, were only increased in CSQ, indicating a possible influence of NCX in the regulation of SR-Ca(2+) uptake proteins. The Ca(2+) transients and the L-type Ca(2+) currents in the presence of caffeine were very large in CSQ, but smaller increases were noted in double transgenic mice. Therefore, the successful co-overexpression of CSQ and NCX in these mice provides a novel model in which to investigate the interaction of proteins tightly linked to maintain Ca(2+) homeostasis.

Animals↗

PubMed1999

Expression of cardiac calcium regulatory proteins in atrium v ventricle in different species.

The duration of contraction in isolated electrically driven preparations from atrium and ventricle of mouse, rat, rabbit, guinea-pig and dog was consistently shorter in atrial compared to ventricular preparations. Overexpression of phospholamban (PLB) in transgenic mice prolonged duration of contraction, underscoring the importance of PLB for kinetics of cardiac contractility. The expression of regulatory proteins was studied by Western and Northern blot analysis. In rat myocardium, expression of the sarcoplasmic reticulum Ca2+ ATPase (SERCA) was higher in atrium than in ventricle, as was also observed in the rabbit, guinea-pig and wild-type mouse samples. Canine myocardium, however, had similar levels of SERCA (protein and mRNA) in atrium and ventricle. PLB and calsequestrin on protein and RNA levels were lower in atrium than in ventricle from rat, rabbit, guinea-pig and wild-type mouse. PLB protein and RNA levels were higher in ventricle than in atrium at ages 1 and 5 days postnatally and in adult rats. SERCA protein and RNA levels were higher in ventricle than in atrium at days 1 and 5 after birth, but lower in ventricle than in atrium in adult rats. In dog, the calsequestrin level was identical in atrium and ventricle (protein and mRNA) and PLB did not differ between atrium vs ventricle at the protein level but was lower at the mRNA level. Also, Ca2+ uptake was higher in atrium than in ventricle in the dog samples. The expression of the inhibitory subunit of troponin was unchanged between atrium and ventricle in all species studied (protein and mRNA). In dog, protein expression of triadin and junctin was lower in atrium vs ventricle. Triadin mRNA was not altered in dog atrium vs ventricle. In summary, while the hastened relaxation of atrium vs ventricle correlates in part with the lower expression of PLB and higher expression of SERCA, altered regional expression of other SR proteins handling Ca2+ may also play an important role in some species.

Animals↗