Monensin-induced Reversal of Positive Force–Frequency Relationship in Cardiac Muscle: Role of Intracellular Sodium in Rest-dependent Potentiation of Contraction

1997 ◽  
Vol 29 (3) ◽  
pp. 977-989 ◽  
Author(s):  
Kanigula Mubagwa ◽  
Wei Lin ◽  
Karin Sipido ◽  
Suzanne Bosteels ◽  
Willem Flameng
Keyword(s):  
Cardiac Muscle ◽  
Intracellular Sodium ◽  
Force Frequency ◽  
Frequency Relationship ◽  
Positive Force

Concealed positive force-frequency relationships in rat and mouse cardiac muscle revealed by ryanodine

1986 ◽  
Vol 251 (6) ◽  
pp. H1106-H1110 ◽  
Author(s):  
P. Stemmer ◽  
T. Akera
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Negative Inotropic Effect ◽  
Ion Concentration ◽  
Mouse Heart ◽  
Force Frequency ◽  
Frequency Relationship ◽  
Negative Relationships ◽  
Modest Effect ◽  
Positive Force

Increases in stimulation frequency between 0.3 and 2 Hz decrease developed tension in rat, seemingly inconsistent with the explanation that an elevation of intracellular Na+-ion concentration is responsible for the positive force-frequency relationships observed in most species. Thus the force-frequency relationships were reevaluated in isolated atrial muscle of rat and mouse heart that show negative relationships, comparing them with ferret and guinea pig that show positive relationships. Ryanodine (2 nM, 45-min exposure) markedly reduced potentiated postrest contractions in all four species and caused a marked negative inotropic effect especially at low stimulation frequencies in rat and mouse, a moderate effect in ferret, but only a modest effect in guinea pig. In the presence of ryanodine, all four species showed positive force-frequency relationships. These results indicate that activator calcium in rat, mouse, and ferret cardiac muscle has a large ryanodine-sensitive component that shows a negative force-frequency relationship, masking a component for positive force-frequency relationships that exists in all species.

Abstract 15596: Maturation of Hipsc-cm Electrophysiological and Contractile Function for Enhanced Sensitivity of Cardiac Safety Assays

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Heather B Hayes ◽  
Anthony M Nicolini ◽  
Colin Arrowood ◽  
Daniel Millard
Keyword(s):  
Contractile Function ◽  
Induced Pluripotent Stem Cell ◽  
Force Frequency ◽  
Cardiac Safety ◽  
Electrophysiological Response ◽  
Mechanical Conditioning ◽  
Enhanced Sensitivity ◽  
Frequency Relationship ◽  
Positive Force

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have significantly advanced in vitro cardiac safety and disese modeling, yet remain an immature representation of human myocytes. Electrical or mechanical conditioning of hiPSC-CMs facilitates functional maturation, as measured by a positive force-frequency relationship, but current in vitro protocols require 2-4 weeks of conditioning. Using array-based contractility and local electrical stimulation, we detected functionally mature phenotypes and compound responses in hiPSC-CMs after only 48 hours of chronic pacing. To mature cardiomyocytes, hiPSC-CMs were cultured on 24- and 96-well MEA plates with a dedicated stimulation electrodes. Later, hiPSC-CMs were electrically or optically paced at 2Hz for 48 hours. Multimodal measures quantified contractile and electrophysiological responses to varied pacing rates and compound addition. After 48 hours of pacing, hiPSC-CMs displayed shortened repolarization timing compared to before chronic pacing (baseline: 423 +/- 21 ms; matured: 316 +/- 15 ms), without significant beat period changes (baseline: 1255 +/- 40 ms; matured: 1314 +/- 84 ms). Contractile beat amplitude was measured using array-based impedance during spontaneous beating and at increasing pacing rates (1, 1.2, 1.5, 2, and 2.5 Hz). Before chronic pacing, beat amplitude decreased with increasing pacing rate; after chronic pacing, the same wells displayed increased beat amplitudes with increasing pacing rate. The matured wells also showed enhanced sensitivity to positive inotropes, such as isoproterenol, digoxin, omecamtiv mecarbil, and dobutamine. Local extracellular action potentials (LEAP) further revealed altered electrophysiological response to ranolazine, a multichannel blocker. Unpaced control wells exhibited dose-dependent APD90 prolongation in response to ranolazine, whereas matured wells showed no APD90 change. Similar results were seen with 48 hour of optogenetic pacing at 2 Hz. Overall, hiPSC-CMs chronically paced for only 48 hours exhibited more mature functional phenotypes, including a positive force-frequnecy relationship, enhanced ionotrope sensitivity, and altered compound response.

Action potential duration and force-frequency relationship in isolated rabbit, guinea pig and rat cardiac muscle

1996 ◽  
Vol 166 (2) ◽  
pp. 150-155 ◽  
Author(s):  
P. Szigligeti ◽  
C. Pankucsi ◽  
T. B�ny�sz ◽  
A. Varr� ◽  
P. P. N�n�si
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Cardiac Muscle ◽  
Action Potential Duration ◽  
Force Frequency ◽  
Frequency Relationship

Effects of rate and rhythm on contraction of rat papillary muscle

1959 ◽  
Vol 197 (6) ◽  
pp. 1199-1204 ◽  
Author(s):  
Brian F. Hoffman ◽  
John J. Kelly
Keyword(s):  
Cardiac Muscle ◽  
Papillary Muscle ◽  
Ionic Composition ◽  
Force Frequency ◽  
Progressive Decrease ◽  
Plasma Epinephrine ◽  
Perfusion Medium ◽  
Frequency Relationship ◽  
Rat Papillary Muscle ◽  
Isolated Rat

The unusual relationship between frequency of contraction and tension developed by the isolated rat papillary muscle has been studied in detail. The progressive decrease in tension with increasing rate is unrelated to the size or weight of the muscle and is not changed by alterations in the ionic composition of the perfusion medium. The force-frequency relationship is also unchanged by addition of plasma, epinephrine or digitalis to the perfusion medium. Rat papillary muscle is similar to other preparations of cardiac muscle with respect to recovery of contractility and the development of rest contractions and postextrasystolic potentiation.

scholarly journals Cardiotoxins from cobra Naja oxiana change the force of contraction and the character of rhythmoinotropic phenomena in the rat myocardium

2019 ◽  
Vol 487 (5) ◽  
pp. 578-583
Author(s):  
A. S. Averin ◽  
M. E. Astashev ◽  
T. V. Andreeva ◽  
V. I. Tsetlin ◽  
Yu. N. Utkin
Keyword(s):  
Positive Inotropic Effect ◽  
Stimulation Frequency ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Rat Myocardium ◽  
Frequency Range ◽  
High Concentration ◽  
Irreversible Damage ◽  
Frequency Relationship ◽  
Positive Force

The study of the influence of cobra Naja oxiana cardiotoxins on the contractility of the rat papillary muscles and its rhythm-inotropic characteristics has that the presence of toxins induces a slight contractility decrease in the stimulation frequency range up to 0,1 Hz. In the stimulation frequency range from 0,1 to 0,5 Hz a positive inotropic effect is found. However, the positive inotropic effect is replaced by a negative one with further increase in the frequency up to 3 Hz. In the presence of cardiotoxins, the positive force-frequency relationship in the region of 1-3 Hz, characteristic of healthy rat myocardium, disappears and relationship becomes completely negative. L‑type calcium channel blocker nifedipine does not affect the changes induced by toxins, while a high concentration (10 mM) of calcium prevents the effects of cardiotoxins on the muscle. The results obtained show that the impairment of the force-frequency relationship occurs long before the development of irreversible damage in the myocardium and may be the first sign of the pathological action of cardiotoxins.

Role of NO and PAF in the impairment of skeletal muscle contractility induced by TNF-α

2000 ◽  
Vol 279 (6) ◽  
pp. R2156-R2163 ◽  
Author(s):  
Giuseppe Alloatti ◽  
Claudia Penna ◽  
Filippo Mariano ◽  
Giovanni Camussi
Keyword(s):  
Skeletal Muscle ◽  
Methyl Ester ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
No Production ◽  
Force Frequency ◽  
Muscle Contractility ◽  
Tnf Α ◽  
Frequency Relationship

The role of platelet-activating factor (PAF) and nitric oxide (NO) as mediators of the effects of tumor necrosis factor-α (TNF-α) on skeletal muscle contractility was studied in guinea pig extensor digitorum longus (EDL) muscle. TNF-α (5–10 ng/ml) reduced contractility at every stimulation frequency (1–200 Hz) and shifted the force-frequency relationship to the right. The role of NO and PAF as mediators of TNF-α was suggested by the protective effect of N G-nitro-l-arginine methyl ester (l-NAME; 1 mM), but not of N G-nitro-d-arginine methyl ester (d-NAME; 1 mM), and by the inhibitory effect of the PAF-receptor antagonist WEB-2170 (3 μM). TNF-α increased the production of PAF and NO. Similar to TNF-α, both S-nitroso- N-acetylpenicillamine (0.5–1 μM), an NO-generating compound, and PAF (10–20 nM) reduced EDL contractility. l-NAME, but not d-NAME, blocked the negative effect of PAF. Blockade of phospholipase A2, which is required for PAF synthesis, significantly reduced the effects of TNF-α. WEB-2170 inhibited NO synthesis induced by TNF-α and PAF-stimulated NO production. These results suggest that both PAF and NO contribute to the development of the mechanical alterations induced by TNF-α and that NO production is downstream to the synthesis of PAF.

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