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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Molecular Cell Research 721 (1982), S. 144-157 
    ISSN: 0167-4889
    Keywords: (Rat heart) ; Ca^2^+ uptake ; Myocardial cell ; Na^+ dependence ; Na^+-Ca^2^+ exchange
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 412 (1988), S. 277-284 
    ISSN: 1432-2013
    Keywords: Isolated cardiac myocytes ; Excitation-contraction coupling ; Cardiac glycosides ; Positive inotropic effect ; Na+−K+ pump ; Na+−Ca2+ exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We used isolated ventricular myocytes to study45Ca2+ transport in the presence of three concentrations of ouabain (10 nM, 1 μM, and 100 μM) in Tyrode solution containing 1 mM CaCl2. The cells were quiescent and during45Ca2+ uptake and45Ca2+ efflux experiments 10 nM ouabain decreased Ca2+ content, 1 μM, didn't change it appreciably, and 100 μM increased it significantly. Qualitatively, the same results were obtained at 22°C and 35°C. Ouabain did not significantly affect the electrical activity of isolated, electrically stimulated myocytes, but it increased the amplitude of shortenings of these myocytes in a dose-dependent manner. Thus, the positive inotropic effect of ouabain at therapeutic doses (≤10 nM) occurs in spite of decreased Ca2+ content, while at high toxic doses the positive inotropic effect is accompanied by an increment in Ca2+ content. These data support the hypothesis that the mechanisms of positive inotropy of ouabain are different at therapeutic and toxic concentrations of this drug. Finally, our study demonstrates that the effects of low doses of ouabain are independent of the release of endogenous catecholamines.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 341 (1973), S. 281-284 
    ISSN: 1432-2013
    Keywords: Contractility ; Voltage Clamp ; Sodium Ions ; Veratrine ; Inotropic Effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Veratrine alkaloids prolong the action potential and exert a positive inotropic effect in frog atrial muscle. In voltage-clamp experiments, veratrine sulphate slowed inactivation of the sodium system, thereby greatly increasing total sodium inward current and also tension; its effect on electrical and mechanical activity was blocked by tetrodotoxin. These findings indicate involvement of sodium ions in the inotropic action of veratrine alkaloids.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2013
    Keywords: Cardiomyopathic hamster (CHF 147) ; M2-muscarinic receptors ; Cardiomyocytes ; [3H]-N-methyl scopolamine ; Micropunches
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously demonstrated that isolated ventricular myocytes from cardiomyopathic hamsters (CHF 147) during the necrotic stage (70–100 days) exhibit an attenuated contractile response to muscarinic stimulation. In the present study we have investigated whether this dysfunction may be related to a change in the density (or affinity) of cardiac muscarinic receptors. Thus, we have characterized and quantified the binding of the muscarinic antagonist [3H]-N-methyl scopolamine (NMS) to M2 muscarinic receptors in cardiac micropunches and in suspensions of isolated intact cardiomyocytes obtained from cardiomyopathic (CHF 147) and Golden Syrian hamsters. The hamsters were either 70–100 days old, when the cardiomyopathy had reached the cytolytic and necrotic stage or 30 days old, i. e. before the onset of the cardiomyopathy. In both preparations (micropunches and dissociated cardiomyocytes) the specific binding of [3H]-NMS was stereospecific, reversible, saturable, of high affinity and linearly dependent upon increasing amounts of tissue and cells. The binding site also possessed the drug specificity typical of an M2 muscarinic receptor. Saturation binding analysis revealed that the hearts of the older CHF 147 hamsters contain significantly fewer M2 muscarinic receptors than the control Golden Syrian hamsters while the affinity (K d) was not altered. This reduction of M2 receptor number was not observed in CHF 147 hamsters at 30 days. Further, we found no differences in β-adrenergic or in α 1-adrenergic binding in the two strains of hamster at either age. Thus, our results indicate that the parasympathetic regulation of cardiac function in CHF 147 hamsters may be compromised by a decreased number of muscarinic receptors at the necrotic stage of the cardiomyopathy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2013
    Keywords: β-Adrenergic receptors ; Isolated cardiomyocytes ; [3H]CGP ; Down-regulation ; β-agonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The major focus of this paper is the characterization and quantification of rat cardiomyocyte, cell-surface β-adrenergic receptors labelled with the hydrophilic radioligand [3H]CGP-12177. The ventricular cardiomyocytes used in these experiments have previously been extensively studied in our laboratory and confirmed to be functionally compatible with similar cells in vivo. Specific binding of [3H]CGP was stereospecific, saturable and of high affinity. Binding of [3H]CGP was also readily reversible, demonstrated appropriate drug specificity and positively correlated with increasing cell concentrations. The potency of the β1-antagonist atenolol was almost 100 times higher than that of the β2-antagonist ICI-118.551 in binding to the [3H]CGP binding site. This preparation appears ideal for the investigation of β-adrenergic receptor regulation in heart cells. Indeed, our initial experiments show clearly that pharmacological concentrations of isoproterenol, and norepinephrine, can reduce (down-regulate) the number of specific [3H]CGP binding sites. This result is in agreement with many other reports on similar experiments in a variety of cell types. However, physiologically relevant concentrations of these two agonists (1–100 nM) do not induce down-regulation of the β-adrenergic receptors in short-term (2 h) incubations. Nevertheless, the high-affinity receptors that we have described mediate a contractile response to isoproterenol in the nanomolar concentration range (EC50 =3.6±0.3 nM). This is approximately 300 times lower than the concentration needed to produce down-regulation. Thus, our data indicate that short-term down-regulation of cardiomyocyte β-adrenergic receptors can only be observed with high, pharmacological concentrations of isoproterenol. In summary, this preparation of cardiomyocytes is wellsuited for the further investigation of (patho)physiological regulation of β-adrenergic receptors.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2013
    Keywords: Isolated cardiac myocytes ; Electrical activity ; Contraction ; Fatty acids ; Ultrastructure ; Diabetes mellitus, experimental ; Streptozotocin ; Electrophysiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of chronic experimental diabetes on electrophysiological properties, contractile behavior,45Ca2+ transport, fatty acid profiles and ultrastructural characteristics were studied in enzymatically dissociated ventricular myocytes. Diabetes was induced in rats by streptozotocin administration and animals were killed 8–10 weeks later. Myocytes from diabetic rats exhibited electrical behavior similar to that of myocytes from control rats, but their contractile properties were altered. Their sensitivity of the twitch contractions to various positive and negative inotropic agents (isoproterenol, norepinephrine, phenylephrine, acetylcholine, ouabain and veratridine) was greatly diminished. However, a part of the contractile response (the tonic, sustained contractions) were increased in the diabetic myocytes, indicating that the changes are not caused by a decreased sensitivity of myofilaments. Furthermore, the diabetic myocytes exhibited also significant decrease in total Ca2+ content. The fatty acid profile in the diabetic group was changed mainly in that there were slightly elevated levels of docosahexaenoic acid and diminished levels of palmitic acid. The ultrastructure of the diabetic myocytes was affected only slightly. These investigations offer for the first time a comprehensive picture of changes related to diabetic cardiomyopathy as they occur at the level of cardiomyocytes.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0878
    Keywords: Key words Choline acetyltransferase ; Tyrosine hydroxylase ; Vasoactive intestinal peptide ; Neuropeptide Y ; Substance P ; Immunofluorescence ; Guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Functional data indicate that neurons in distinct regions of the heart exert preferential regional cardiac control. To date the regional distribution of specific types of neurons within the intrinsic cardiac nervous system remains unknown, as does their associations with distinct neurotransmitter and/or neuromodulatory profiles. This study was designed to ascertain: (1) the distribution of different classes of neurons within the intrinsic cardiac nervous system as determined by microscopic analysis; (2) the neurochemical profiles of neurons in differing atrial loci; (3) which neurochemicals are co-localized within specific populations of intrinsic cardiac neurons; and (4) the distribution of specific sub-populations of neurons expressing specific immunoreactivities. Taking advantage of confocal laser scanning microscopy and distinct immunoreactive fluorescent markers in various double-label combinations, several sub-populations of intrinsic cardiac neurons were identified. Of all identified neurons, 85–90% were located in ganglia (ganglionic neurons), the rest being isolated (individual neurons). The two general neuronal markers protein gene product 9.5 (PGP 9.5) and microtubule-associated protein (MAP-2) were associated with neurons clustered primarily in the interatrial septum and around the origins of the two vena cavae. Ganglia (group 1) contained three sub-populations of neurons: approx. 80% of ganglionic neurons were large (15–40 µm diameters; group 1a) and approx. 20% had smaller diameters (less than 15 µm; group 1b). All of these neurons were PGP-immunoreactive, exhibiting choline acetyltransferase (ChAT) immunoreactivity (IR), tyrosine hydroxylase (TH) IR, neuropeptide Y (NPY) IR, vasoactive peptide (VIP) IR and substance P (SP) IR. The remaining 5% of ganglionic neurons were small (group 1c; less than 20 µm). These displayed TH immunoreactivity but not MAP, PGP, CHAT, NPY or SP immunoreactivity. Ten to fifteen percent of all neurons loosely distributed outside of ganglia were small (10–25 µm) and located primarily around the origin of the superior vena cava. They displayed immunoreactivity to TH, ChAT, VIP, NPY and SP, but not to MAP-2 or PGP 9.5. These data provide anatomical and immunohistochemical evidence for specific localization of differing populations of intrinsic cardiac neurons with respect to their size, ganglionic distributions and capacity to express multiple neurotransmitters. Although the functional importance of such a regional distribution of differing populations of intrinsic cardiac neurons remains unknown, these anatomical data support the thesis that unique clustering of specific populations of neurons within this nervous system represents the anatomical substrate for complex local cardiac regulatory phenomena occurring at the level of the target organ.
    Type of Medium: Electronic Resource
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