Characterization of the inotropic response induced by stimulation of β-adrenergic and H1 histaminergic receptors in guinea pig left atria

1978 ◽  
Vol 56 (6) ◽  
pp. 926-933 ◽  
Author(s):  
Thomas E. Tenner Jr. ◽  
John H. McNeill
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Narrow Range ◽  
The Other ◽  
Inotropic Response ◽  
Receptor Stimulation ◽  
Experimental Conditions ◽  
High Frequencies ◽  
Stimulation Of

The inotropic response induced by β-adrenergic and H1 histaminergic receptor stimulation was characterized in guinea pig left atria by obtaining dose–response relationships for isoproterenol and histamine under various experimental conditions. Conditions (hypothermia, high frequencies of stimulation, and large extracellular calcium concentrations) which enhanced the ability of cardiac muscle to develop force also increased the sensitivity of the left atrium to isoproterenol while decreasing its efficacy. On the other hand, conditions which enhanced the ability of cardiac muscle to develop force depressed the efficacy of histamine to such an extent that the sensitivity to histamine was also decreased. In addition, conditions which markedly depressed the ability of cardiac muscle to develop force also decreased the efficacy and sensitivity to histamine. The data indicate that while β-adrenoceptor stimulation results in an inotropic response under all conditions studied, stimulation of H1 histaminergic receptors results in an inotropic response only within a narrow range of experimental conditions.

scholarly journals The structure of the native cardiac thin filament at systolic Ca2+ levels

2021 ◽  
Vol 118 (13) ◽  
pp. e2024288118
Author(s):  
Cristina M. Risi ◽  
Ian Pepper ◽  
Betty Belknap ◽  
Maicon Landim-Vieira ◽  
Howard D. White ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Binding Sites ◽  
Short Range ◽  
Bound States ◽  
Thin Filament ◽  
Narrow Range ◽  
The Other ◽  
Thin Filaments ◽  
Troponin Complex ◽  
Myosin Binding

Every heartbeat relies on cyclical interactions between myosin thick and actin thin filaments orchestrated by rising and falling Ca2+ levels. Thin filaments are comprised of two actin strands, each harboring equally separated troponin complexes, which bind Ca2+ to move tropomyosin cables away from the myosin binding sites and, thus, activate systolic contraction. Recently, structures of thin filaments obtained at low (pCa ∼9) or high (pCa ∼3) Ca2+ levels revealed the transition between the Ca2+-free and Ca2+-bound states. However, in working cardiac muscle, Ca2+ levels fluctuate at intermediate values between pCa ∼6 and pCa ∼7. The structure of the thin filament at physiological Ca2+ levels is unknown. We used cryoelectron microscopy and statistical analysis to reveal the structure of the cardiac thin filament at systolic pCa = 5.8. We show that the two strands of the thin filament consist of a mixture of regulatory units, which are composed of Ca2+-free, Ca2+-bound, or mixed (e.g., Ca2+ free on one side and Ca2+ bound on the other side) troponin complexes. We traced troponin complex conformations along and across individual thin filaments to directly determine the structural composition of the cardiac native thin filament at systolic Ca2+ levels. We demonstrate that the two thin filament strands are activated stochastically with short-range cooperativity evident only on one of the two strands. Our findings suggest a mechanism by which cardiac muscle is regulated by narrow range Ca2+ fluctuations.

scholarly journals Physics Augmented U-Net: A High-Frequency Aware Generative Prior for Microscopy

2021 ◽  
Author(s):  
Jathurshan Pradeepkumar ◽  
Mithunjha Anandakumar ◽  
Vinith Kugathasan ◽  
Andrew Seeber ◽  
Dushan N Wadduwage
Keyword(s):  
High Frequency ◽  
Forward Model ◽  
The Other ◽  
Structured Illumination ◽  
Structured Illumination Microscopy ◽  
Experimental Conditions ◽  
Low Frequencies ◽  
High Frequencies ◽  
Proposed Model ◽  
Microscopy Images

A key challenge in optical microscopy is to image fast at high-resolution. To address this problem, we propose "Physics Augmented U-Net", which combines deep learning and structured illumination microscopy (SIM). In SIM, the structured illumination aliases out-of-band high-frequencies to the passband of the microscope; thus SIM captures some high-frequencies even when the image is sampled at low-resolution. To utilize these features, we propose a three-element method: 1) a modified U-Net model, 2) a physics-based forward model of SIM 3) an inference algorithm combining the two models. The modified U-Net architecture is similar to the seminal work, but the bottleneck is modified by concatenating two latent vectors, one encoding low-frequencies (LFLV), and the other encoding high-frequencies (HFLV). LFLV is learned by U-Net contracting path, and HFLV is learned by a second encoding path. In the inference mode, the high-frequency encoder is removed; HFLV is then optimized to fit the measured microscopy images to the output of the forward model for the generated image by the U-Net. We validated our method on two different datasets under different experimental conditions. Since a latent vector is optimized instead of a 2D image, the inference mode is less computationally complex. The proposed model is also more stable compared to other generative prior-based methods. Finally, as the forward model is independent of the U-Net, Physics Augmented U-Net can enhance resolution on any variation of SIM without further retraining.

CORTICOID PRODUCTION IN VITRO AS A TEST OF ADRENOCORTICAL FUNCTION IN RATS

1960 ◽  
Vol XXXIII (I) ◽  
pp. 59-66 ◽  
Author(s):  
J. van der Vies
Keyword(s):  
Adrenal Cortex ◽  
Adrenal Function ◽  
The Other ◽  
Adrenocortical Function ◽  
Experimental Conditions ◽  
Adrenal System ◽  
Other Hand ◽  
Stimulation Of

ABSTRACT Adrenal function in rats under various experimental conditions was studied by incubating the adrenals in vitro and determining the corticosteroid output during one hour. This in vitro corticoid production was reduced after hypophysectomy, hypothalamus-lesioning and treatment with hydrocortisone or with Nembutal and morphine. On the other hand, an increased production was observed following stimulation of the pituitary-adrenal system by exogenous histamine or corticotrophin. From these experiments it is concluded that the corticoid production in vitro reflects the activity of the adrenal cortex in vivo and hence can be used for the study of the latter function.

Characterization of the histamine receptors in rabbit left atria

1981 ◽  
Vol 59 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Alicia Polanin ◽  
John H. McNeill
Keyword(s):  
Left Atrial ◽  
Histamine Receptor ◽  
Histamine Receptors ◽  
Receptor Blockade ◽  
Inotropic Response ◽  
Receptor Stimulation ◽  
Inotropic Effects ◽  
Receptor Antagonism ◽  
Positive Inotropic Effects

The effects of selective histamine receptor analogs were studied in electrically paced rabbit left atria. Atrial tension was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA) (an H1 agonist). The responses to histamine and impromidine were not altered by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the responses to 4-methylhistamine and PEA were significantly decreased upon pretreatment with propranolol or reserpine. Promethazine pretreatment (H1 receptor blockade) antagonized the inotropic effects of histamine and PEA but had no effect on the responses to 4-methylhistamine or impromidine. Cimetidine pretreatment (H2 receptor antagonism) competitively blocked the positive inotropic effects of histamine, 4-methylhistamine, and impromidine. These results suggest that the left atrial inotropic response is mediated through H1 and H2 receptor stimulation.

scholarly journals Muscarinic-receptor stimulation enhances polyphosphoinositide breakdown in guinea-pig ileum smooth muscle

1984 ◽  
Vol 223 (2) ◽  
pp. 527-531 ◽  
Author(s):  
M C Sekar ◽  
B D Roufogalis
Keyword(s):  
Guinea Pig ◽  
Muscarinic Receptor ◽  
Longitudinal Muscle ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Exchange Chromatography ◽  
Guinea Pig Ileum ◽  
Receptor Stimulation ◽  
Inositol 1 ◽  
Stimulation Of

Muscarinic-receptor stimulation by 0.1 mM-carbachol in longitudinal muscle of the guinea-pig ileum increases the incorporation of [3H]inositol into inositol-containing phospholipid. This effect was blocked by 16 microM-atropine. After 60 min incubation, carbachol increased the accumulation of total inositol phosphates 20-fold in the presence of 10 mM-Li+. Less than 20% of the total inositol phosphate corresponded to inositol 1-phosphate by ion-exchange chromatography, whereas of the remainder about two-thirds corresponded to inositol bisphosphate and one third to inositol trisphosphate. It is concluded that stimulation of muscarinic receptors in guinea-pig ileum enhances breakdown of polyphosphoinositides, suggesting that this may be a primary event associated with Ca2+ mobilization in the guinea-pig ileum.

Ca2+dependence of positive inotropic responses of guinea pig isolated cardiac preparations to cAMP-generating and cAMP-independent agonists

1984 ◽  
Vol 62 (1) ◽  
pp. 105-108 ◽  
Author(s):  
L. F. Yao ◽  
K. M. MacLeod ◽  
J. H. McNeill
Keyword(s):  
Guinea Pig ◽  
Papillary Muscles ◽  
Similar Magnitude ◽  
Myocardial Cells ◽  
Receptor Stimulation ◽  
Histamine Response ◽  
Β Receptor ◽  
Inotropic Responses ◽  
Stimulation Of

The effects of procedures which diminish Ca2+ influx into myocardial cells on responses of isolated cardiac preparations to cAMP-independent histamine H1 receptor stimulation and cAMP-generating β-receptor stimulation were measured. The histamine response of guinea pig left atria, which appears to be primarily mediated by H1 receptors, was depressed to a greater extent than was the response of this preparation to isoproterenol by decreasing the extracellular Ca2+ concentration, and by the Ca2+ influx blocker D-600. Similarly, while the H1 agonist 2-pyridylethylamine dihydrochloride (PEA) produced increases in tension of a similar magnitude as the partial β-agonist salbutamol in both left atria and in papillary muscles, responses of both preparations to PEA were depressed to a significantly greater extent by decreasing the extracellular Ca2+ concentration than were responses to salbutamol. Overall, both the basal developed force of papillary muscles and the responses of these preparations to H1 and β-receptor stimulation appeared to be less depressed by decreasing the extracellular Ca2+ concentration than were those of left atria. These results indicate that responses mediated via cAMP-independent H1 receptors, like those arising from α-receptor stimulation, are more sensitive to procedures which diminish Ca2+ influx than are responses arising from stimulation of cAMP-generating β-receptors. This may reflect differences in the mechanisms by which stimulation of H1, α-, and β-receptors give rise to positive inotropic responses. In addition, left atria may be more dependent than papillary muscles on extracellular Ca2+ for the support of contraction.

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