Age-dependent changes in electrophysiologic characteristics of fast and slow action potentials in rat papillary muscle

1983 ◽  
Vol 61 (12) ◽  
pp. 1509-1515 ◽  
Author(s):  
Michio Kojima ◽  
Nick Sperelakis ◽  
Gordon Johnson ◽  
Stewart Ehrreich ◽  
Tibor Balazs

Isolated papillary muscles from juvenile (about 2 months old, average weight of 250 g) and young adult rats (about 4 months old, average weight 485 g) were studied for age-dependent differences in the characteristics of fast and slow action potentials (APs). The fast and slow APs were recorded in 5.4 mM and 25 mM K+-Tyrode solutions, respectively (stimulation rate of 1 Hz). For the slow APs, the dose–response curves for isoproterenol versus [Formula: see text] (the maximum rate of rise of the APs), overshoot, and AP amplitude were linear between 10−9 M and 10−6 M (10−5 M in some cases) in the juvenile and young adult rats. Isoproterenol pretreatment (1 mg/kg s.c, 1 h prior) decreased the slope of the dose–response curve, and saturation was achieved at a lower concentration. The [Formula: see text], overshoot, and amplitude of both the fast and slow APs were somewhat smaller in the young adult rats than in the juvenile rats; there were no differences in the resting potential, AP duration, or threshold voltage. These results suggest that activation of a greater fraction of the β-adrenergic receptors is coupled directly or indirectly to activation of a greater fraction of the slow channels. The pretreatment data suggest that down-regulation of the β-adrenergic receptor may occur. The conductance per channel for the fast Na+ channels and slow channels, and (or) the number of both types of functional channels, may decrease with age.

1983 ◽  
Vol 244 (3) ◽  
pp. H454-H457
Author(s):  
M. T. Knabb ◽  
R. Rubio ◽  
R. M. Berne

The effects of endogenous adenosine on rat atrial and ventricular slow action potentials (AP) were studied using theophylline, an adenosine receptor antagonist, or "micro" adenosine deaminase (mADA), small polypeptides having adenosine deaminase activity. Exogenous adenosine (10(-6) M) depressed slow APs at low and high isoproterenol concentrations and shifted the isoproterenol dose-response curve to the right in the atrium. In the ventricle, exogenous adenosine inhibited slow APs at low isoproterenol doses and only shifted the bottom of the dose-response relationship to the right. mADA (0.84 U) or theophylline (5 X 10(-5) M) potentiated the response to threshold concentrations of isoproterenol and caused a parallel shift of the curve to the left in the atrium but only shifted the bottom portion of the curve in the ventricle. This potentiation of slow APs in the presence of mADA or theophylline suggests that endogenous adenosine attenuates the response to isoproterenol in cardiac muscle.


1983 ◽  
Vol 61 (9) ◽  
pp. 957-966 ◽  
Author(s):  
Tung Li ◽  
Nick Sperelakis

The effects of four Ca antagonists, bepridil, diltiazem, nifedipine, and verapamil, on slow channels were studied in cultured cell reaggregates prepared from 14-day-old chick embryonic, hearts. The cell membrane was partially depolarized to about −45 mV by using 22 mM KCl to inactivate the fast Na+ channels. Slow action potentials were induced by 10−6 M isoproterenol with electrical stimulation. Cumulative dose – response curves for the effect of the four drugs on the blocking of slow action potentials (using [Formula: see text] as the indicator) were analyzed by Hill plots. The dose values for 50% of maximal effect, at a stimulation frequency of 60/min, were (in order of decreasing potencies) as follows: 5.2 × 10−9 M for nifedipine, 3.1 × 10−7 M for diltiazem, 1.2 × 10−6 M for verapamil, and 5.1 × 10−6 M for bepridil. The effect of all four Ca antagonists showed use (or frequency)-dependency, i.e., the drugs were more effective at higher stimulation rates. This may reflect a blocking action of the drugs on the nonresting states of the channels and (or) a slowing of the recovery kinetics of the channels from the inactivated state back to the resting state. In a separate type of experiment utilizing a 5-min rest period in the presence of the drugs, nifedipine blocked and bepridil exhibited some depression of the first action potential elicited, i.e., use-independent effect, indicating that these drugs may also act on resting channels. Thus, these four Ca antagonists have a prominent use-dependent component in their actions, and one or two may also have a use-independent component.


1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.


1991 ◽  
Vol 65 (02) ◽  
pp. 160-164 ◽  
Author(s):  
Marina Poggio ◽  
Armando Tripodi ◽  
Guglielmo Mariani ◽  
Pier Mannuccio Mannucci ◽  

SummaryBeing a putative predictor of ischemic heart disease, the measurement of factor VII (FVTI) coagulant activity will be presumably requested to clinical laboratories with increasing frequency. To assess the influence on FVII assays of different thromboplastins and FVII-deficient plasmas we compared performances of all possible combinations of 5 thromboplastins and 6 deficient plasmas. The reproducibility of the clotting times of the dose-response curves for human and rabbit thromboplastins were acceptable (CV lower than 7%), whereas bovine thromboplastin had a higher CV. Reproducibility was very similar for all deficient plasmas when they were used in combination with a given thromboplastin. Responsiveness of the dose-response curve did not depend on the deficient plasma but rather on the thromboplastin: one rabbit thromboplastin was the least responsive, the bovine thromboplastin the most responsive, the human and the remaining two rabbit thromboplastins had intermediate responsiveness. Assay sensitivity to cold-activated FVII varied according to the thromboplastin: the bovine thromboplastin was the most sensitive, the human thromboplastin the least sensitive, of the three rabbit thromboplastins two were relatively sensitive, one was almost insensitive. In conclusion, our results indicate that thromboplastin rather than deficient plasma is the crucial factor in the standardization of FVII assay.


1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.


1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.


1963 ◽  
Vol 42 (1) ◽  
pp. 29-38 ◽  
Author(s):  
L. Ther ◽  
H. Schramm ◽  
G. Vogel

ABSTRACT Longitudinal tension exerted on a killed rat's femur results always in rupture on the same place viz: the distal epiphyseal line. The power required to produce this effect can be measured with a simple dynamometer. The tensile strength increases with advancing age and during exsiccation (thirst). In untreated rats (weight range 100–120 g) this value amounts to about 1.5–1.8 kg. Tensile strength of the femoral epiphyseal line may be influenced by hormones. Corticosteroids such as prednisolone acetate and cortisol acetate increase the level of maximal load to more than 2.0 kg. In general the effect of a single injection reaches a climax after 48 hours. Dose-response-curves can be established and relative effectiveness may be gathered therefrom. Deoxycorticosterone acetate likewise increases tensile strength in spite of the fact that contrary to prednisolone exhibiting diuretic action this compound has a water retaining effect. Triiodothyronine and progesterone when given alone produce a slight decrease in tensile strength. The effect of prednisolone when given simultaneously with one of these two compounds is antagonized: this phenomenon is more pronounced in the case of triiodothyronine.


2005 ◽  
Vol 8 (4) ◽  
pp. E269-E274 ◽  
Author(s):  
Sydney L. Gaynor ◽  
Gregory D. Byrd ◽  
Michael D. Diodato ◽  
Yosuke Ishii ◽  
Anson M. Lee ◽  
...  

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