Effects of Anions on Frog Ventricle

1973 ◽  
Vol 51 (10) ◽  
pp. 709-726 ◽  
Author(s):  
Esther R. Anderson ◽  
J. G. Foulks
Keyword(s):  
Mechanical Properties ◽  
Action Potential ◽  
Time Course ◽  
Frog Heart ◽  
Resting Membrane Potential ◽  
Tension Development ◽  
Action Potential Prolongation ◽  
Frog Ventricle ◽  
Slow Onset ◽  
Contractile Performance

The effects of replacement of external chloride by other anions on the electrical and mechanical properties of frog ventricular muscle have been studied.The effects of methylsulfate were similar to those expected for replacement of a permeant anion with an impermeant anion. Increased twitch tension was largely dependent on action potential prolongation. Other anions of the sulfate–sulfonate series produced similar changes, but minor differences in their actions indicated that their effects could not be explained entirely by the elimination of chloride current.Acetate and its analogues produced dramatic changes in both the electrical and mechanical properties of frog heart. All caused a marked hyperpolarization of the resting membrane potential, accompanied by characteristic changes in the shape and duration of the repolarization phase of the action potential. Enhanced contractile performance was characterized by an increased rate of tension development and a slow onset of relaxation. These effects were equally prominent upon transfer to acetate Ringer's solution after previous equilibration to a medium containing methylsulfate in place of chloride. Although similar qualitatively, the members of this series of anions also displayed marked quantitative differences in the intensity and time course of their effects.

Analysis of catecholamine effects in single atrial trabeculae of the frog heart

1977 ◽  
Vol 197 (1128) ◽  
pp. 333-362 ◽  
Keyword(s):  
Cell Membrane ◽  
Action Potential ◽  
Time Course ◽  
Drug Exposure ◽  
Drug Application ◽  
Latency Period ◽  
Frog Heart ◽  
Phosphodiesterase Activity ◽  
Inward Current ◽  
Calcium Inward Current

A study was made of the time course of the effects of adrenaline and isoprenaline on both twitch tension and the intracellular action potential of single atrial trabeculae from frog heart, under a variety of experimental conditions. Twitch tension and overshoot of action potentials rose and subsided in a parallel fashion during build-up and decline of catecholamine action. Cessation of stimulation during drug application had little effect on the tension responses to the drugs. These, and also results obtained with step changes of external calcium concentration during drug exposure, suggest that tension enhancement is a direct consequence of the increased calcium inward current produced by the catecholamines. Exceptional results from trabeculae of ‘hypodynamic’ hearts are described and interpreted on the basis of previous findings obtained in the ‘hypo-dynamic’ condition. Under suitable conditions, including the use of brief periods of drug exposure (≤20 s), three phases of ( β -catecholamine action were discernible: (1) a latency period, of up to 15 s, which preceded tension and potential rise after drug application. Results are presented suggesting that this latency mainly reflects the time which it takes for drug-combined receptors to activate adenylate cyclase in the cell membrane. (2) A sub­sequent phase was critically dependent, in both its magnitude and time course, on phosphodiesterase activity, as was shown by the application of the specific inhibitors papaverine, ICI 63 197, and Ro 20-1724. This phase is probably controlled by the build-up and decline of cAMP within the cells and the subsequent activation and deactivation of a protein kinase. (3) A third phase, associated with the final portion of the decline of catecholamine action, was relatively insensitive to moderate inhi­bition of phosphodiesterase activity. It is attributed to a change of phosphorylation of sites at the internal surface of the cell membrane, the process which, it is assumed, determines the size of calcium inward current during an action potential. Tension decline after a short staircase occurred with a time course closely similar to that of the final phase of the declining catecholamine response. A common final step in the sequential cellular processes under­ lying the two responses is proposed. In some 40% of the trabeculae examined, adrenaline responses were of ‘mixed’ origin: in addition to the relatively slow β -adrenergic action, an initial rapid tension change was present, and experimental tests suggest that this is mediated by α -type receptors.

scholarly journals Clearance of Extracellular K+ during Muscle Contraction—Roles of Membrane Transport and Diffusion

2008 ◽  
Vol 131 (5) ◽  
pp. 473-481 ◽  
Author(s):  
Torben Clausen
Keyword(s):  
Extracellular Space ◽  
Time Course ◽  
Inhibitory Effects ◽  
Tension Development ◽  
Tetanic Force ◽  
New Information ◽  
Significant Difference ◽  
Force Recovery ◽  
Transport And Diffusion ◽  
Contractile Performance

Excitation of muscle often leads to a net loss of cellular K+ and a rise in extracellular K+ ([ K+ ]o), which in turn inhibits excitability and contractility. It is important, therefore, to determine how this K+ is cleared by diffusion into the surroundings or by reaccumulation into the muscle cells. The inhibitory effects of the rise in [K+ ]o may be assessed from the time course of changes in tetanic force in isolated muscles where diffusional clearance of K+ is eliminated by removing the incubation medium and allowing the muscles to contract in air. Measurements of tetanic force, endurance, and force recovery showed that in rat soleus and extensor digitorum longus (EDL) muscles there was no significant difference between the performance of muscles contracting in buffer or in air for up to 8 min. Ouabain-induced inhibition of K+ clearance via the Na+,K+ pumps markedly reduced contractile endurance and force recovery in air. Incubation in buffer containing 10 mM K+ clearly inhibited force development and endurance, and these effects were considerably reduced by stimulating Na+,K+ pumps with the β2-agonist salbutamol. Following 30–60 s of continuous stimulation at 60 Hz, the amount of K+ released into the extracellular space was assessed from washout experiments. The release of intracellular K+ per pulse was fourfold larger in EDL than in soleus, and in the two muscles, the average [K+ ]o reached 52.4 and 26.0 mM, respectively, appreciably higher than previously detected. In conclusion, prevention of diffusion of K+ from the extracellular space of isolated working muscles causes only modest interference with contractile performance. The Na+,K+ pumps play a major role in the clearance of K+ and the maintenance of force. This new information is important for the evaluation of K+-induced inhibition in muscles, where diffusional clearance of K+ is reduced by tension development sufficient to suppress circulation.

Physiological properties of primate lumbar motoneurons

1992 ◽  
Vol 68 (4) ◽  
pp. 1121-1132 ◽  
Author(s):  
J. S. Carp
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Cell Size ◽  
Current Pulse ◽  
Time Course ◽  
Triceps Surae ◽  
Resting Membrane Potential ◽  
Action Potential Amplitude ◽  
Lateral Gastrocnemius ◽  
Potential Amplitude

1. Intracellular recordings were obtained from 149 motoneurons innervating triceps surae (n = 109) and more distal muscles (n = 40) in 14 pentobarbital-anesthetized monkeys (Macaca nemestrina). The variables evaluated were resting membrane potential, action potential amplitude, conduction velocity (CV), input resistance (RN), membrane time constant (tau m), electrotonic length (L), whole-cell capacitance (Ctot), long current pulse threshold (rheobase), short current pulse threshold (Ishort), afterhyperpolarization (AHP) maximum amplitude (AHPmax), AHP duration (AHPdur), time to half maximum AHP amplitude (AHP t1/2), depolarization from resting potential to elicit action potential (Vdep), and threshold voltage for action potential discharge (Vthr). 2. Mean values +/- SD for the entire sample of motoneurons are as follows: resting membrane potential -67 +/- 6 mV; action potential amplitude 75 +/- 7 mV; CV 71 +/- 6 m/s; RN 1.0 +/- 0.5 M omega; tau m 4.4 +/- 1.5 ms; L 1.4 +/- 0.2 lambda; Ctot 7.1 +/- 1.8 nF; rheobase 13 +/- 7 nA; Ishort 29 +/- 14 nA; AHPmax 3.5 +/- 1.3 mV; AHPdur 77 +/- 26 ms; AHP t 1/2 21 +/- 7 ms; Vdep 11 +/- 4 mV; and Vthr -56 +/- 5 mV. CV is lower in soleus than in either medial or lateral gastrocnemius motoneurons, and RN is lower and tau m is longer in soleus than in lateral gastrocnemius motoneurons. 3. RN is higher in motoneurons with longer tau m and slower CV. A linear relationship exists between log(CV) and log(1/RN) with a slope of 1.8-2.2 (depending on the action potential amplitude acceptance criteria used), suggesting that membrane resistivity (Rm) does not vary systematically with cell size. 4. Rheobase is higher in motoneurons with lower RN, longer tau m, shorter AHP time course, and higher CV. Ishort and normalized rheobase (i.e., rheobase/Ctot) vary similarly with these motoneuron properties, except that Ishort is independent of tau m and normalized rheobase is independent of CV. 5. Vthr tends to be more depolarized in motoneurons with large Ctot, but the relationship is sufficiently weak so that any systematic variation in Vthr according to cell size probably contributes only minimally to recruitment order. Vthr does not vary systematically with CV, AHP time course, RN, or tau m. 6. Quantitative differences between macaque and cat triceps surae motoneurons are apparent in CV, which is slower in macaque than in cat, and to a lesser extent in tau m and RN, which are lower in macaque than in cat.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals On the effects of divalent cations and ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetate on action potential duration in frog heart.

1978 ◽  
Vol 71 (1) ◽  
pp. 47-67 ◽  
Author(s):  
D J Miller ◽  
A Mörchen
Keyword(s):  
Ethylene Glycol ◽  
Action Potential ◽  
Calcium Ions ◽  
Action Potentials ◽  
Time Course ◽  
Divalent Cations ◽  
Potassium Conductance ◽  
Resting Potential ◽  
Slow Inward Current ◽  
Frog Heart

Resting and action potentials were recorded from superfused strips of frog ventricle. Reducing the bathing calcium concentration ([Ca2+]0) with or without ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA) prolongs the action potential (AP). The change in the duration of the AP extends over many minutes, but is rapidly reversed by restoring calcium ions. Other changes (e.g., in resting potential and overshoot) are, however, only more slowly reversed. Reducing [Ca2+]0 with 0.2, 2, or 5 mM EGTA produces progressively greater prolongation of AP; maximum values were well in excess of 1 min. This prolongation can be reversed by other divalent cations in EGTA (Mg2+, Sr2+) or Ca-free (Mn2+) solutions, or by acetylcholine. Barium ions increase AP duration in keeping with their known effect on potassium conductance. D600, which blocks the slow inward current in cardiac muscle, is without effect on the action potentials recorded in EGTA solutions, or on the time course and extent of the recovery to normal duration upon restoring calcium ions. It is concluded that divalent cations exert an influence on membrane potassium conductance extracellularly in frog heart. The cell membrane does not become excessively "leaky" in EGTA solutions.

Mechanism of the Effect of Acetate on Frog Ventricular Muscle

1974 ◽  
Vol 52 (3) ◽  
pp. 404-423 ◽  
Author(s):  
Esther R. Anderson ◽  
J. G. Foulks
Keyword(s):  
Membrane Potential ◽  
Resting Membrane Potential ◽  
Acetate Solution ◽  
Tension Development ◽  
Electrogenic Transport ◽  
K Concentration ◽  
Reduced Rate ◽  
Induced Changes ◽  
The Relationship ◽  
Frog Ventricle

Substitution of acetate for external Cl produced a large persistent increase in the resting membrane potential (R.M.P.) of frog ventricle and a somewhat steeper relation between membrane potential (M.P.) and [K]o (external K concentration). An increased K conductance or reduced permeability to other ions could account for most of these results, but not for hyperpolarizations as great as −110 mV. Potentials of this size suggested a contribution from an active electrogenic transport system, but they were unaffected by several treatments including exposure to ouabain (10−7 M − 5 × 10−6 M), dinitrophenol (10−6 M, 10−5 M) or 30 mM tetraethylammonium.Acetate caused a prolongation of the action potential (A.P.) and a change in its configuration. Acetate also enhanced twitch tension and increased the rate of tension development. Similar changes are produced by removal of [K]o. The effects of both acetate and K removal on A.P. configuration were prevented by a reduced rate of stimulation.When acetate-induced hyperpolarization was reversed by raising [K]o to 10–15 mM, the configuration of the A.P. resembled that of controls and twitch tension did not increase. Thus, acetate-induced changes in the shape of the A.P. and in twitch tension appeared to be secondary to the increase in R.M.P. However, the relationship does not seem to be direct because these changes were temporary, whereas hyperpolarization was persistent.The character of the acetate-induced changes in A.P. configuration, and the dependence on stimulation rate and [Ca]o (external Ca concentration), suggested a raised [Ca]i (internal Ca concentration) and a possible increase in Ca influx. However, addition of Mn to the acetate solution did not prevent initial acetate-induced changes in the shape of the A.P. plateau and in twitch tension. Also in the absence of [Ca]o, disappearance of twitch tension was slowed by acetate. But acetate decreased the contracture tension produced in response to either increased [K]o or Na removal. Acetate may cause a redistribution of Ca within the cell.

Cellular mechanisms of early tachycardia-induced ventricular dysfunction in the human heart

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Knierim ◽  
S Pabel ◽  
M Paulus ◽  
P Rainer ◽  
D Scherr ◽  
...  
Keyword(s):  
Relaxation Time ◽  
Action Potential ◽  
Human Heart ◽  
Time Course ◽  
Ventricular Dysfunction ◽  
Myocardial Dysfunction ◽  
Human Myocardium ◽  
Resting Membrane Potential ◽  
Funding Source

Abstract Background Tachycardia-induced cardiomyopathy (TCM) is a reversible form of ventricular dysfunction caused by persistent tachycardia. Characterization of TCM is mainly based on artificially RV paced animal models. Moreover, the underlying mechanisms and time course from compensation to failure remain unclear. This study aimed to investigate early cellular remodeling of tachycardia-induced myocardial dysfunction in human myocardium. Methods and results To elucidate early cellular electrophysiological targets mediating the transition to TCM, we chronically paced (120bpm vs 60bpm control) human induced pluripotent stem cell cardiomyocytes (hiPS-CM) for up to 7d. As a major substrate of cellular myocardial dysfunction, we investigated the influence of chronic tachycardia on cellular Ca cycling. After 24h of persistent tachycardia we detected a significant decrease in Ca transient (CaT) amplitude and reduced diastolic Ca levels (Fura-2). Meanwhile, Ca elimination time (RT80) was unchanged compared to control (n=44/42 cells / 8 diff.). Caffeine application was performed to evaluate sarcoplasmic reticulum (SR) Ca load. We found a shortening of caffeine-induced CaT relaxation time, whereas SR Ca load was unchanged (n=12/13 /8). Further illustrating the transition to TCM, CaT amplitude was progressively decreased after 7d of chronic tachycardia. In contrast to 24h of tachycardia, 7d persistent stimulation resulted in slowed relaxation (RT80, n=75/65 /7). These findings could be explained by a significant reduction of SERCA activity (Ksys-Kcaff) and SR Ca load (n=14/12 / 7). Diastolic Ca concentration remained reduced (n=75/65 /7), in total suggesting a shift to transsarcolemmal Ca elimination. Sodium measurements (SBFI) revealed a significant increase of intracellular sodium concentration (n=69/69 /5) after 7d of tachycardia. In patch clamp experiments we detected a prolongation of action potential duration as early as 24h after onset of tachycardia (n=26/21 /4), which persisted throughout 7d of pacing (n=8/12 /3). Resting membrane potential and action potential amplitude were not changed. Finally, we investigated tachycardia-mediated effects on pre-existing human heart failure (HF). 8h tachycardic stimulation (120bpm) of human HF ventricular trabeculae compromised systolic force, while diastolic tension and relaxation time were markedly increased compared to control (60bpm) (n=7/6 trabeculae /6 human hearts). The extensive molecular characterization of involved ion channels and pathways mediating transition to TCM is currently under investigation. Conclusion This study demonstrates that a persistent tachycardia adversely alters cardiomyocyte excitation-contraction coupling via early electrophysiological cellular remodeling. In pre-existing HF persistent tachycardia strongly aggravates ventricular dysfunction. Our first translational investigation in human myocardium may help to understand the pathophysiology of an underrated and very prevalent disease. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Else-Kröner-Fresenius-Stiftung

Kinetics of procaine-acetylcholine antagonism

1963 ◽  
Vol 204 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Floyd E. Bloom ◽  
Gordon M. Schoepfle
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Time Course ◽  
External Surface ◽  
Complete Recovery ◽  
Rapid Onset ◽  
Resting Membrane Potential ◽  
Nerve Membrane ◽  
Time Parameters ◽  
Kinetics Of

The depression in action potential induced by procaine can be arrested or even reversed by acetylcholine in the previously eserinized frog sciatic single fiber preparation. The extent and time course of the reversal are related to the relative concentrations of both procaine and acetylcholine and to the duration of the previous procaine exposure. Resting membrane potential is not affected. Repeated exposures to procaine are characterized by increasingly rapid onset of block, reduced susceptibility to actylcholine competition, and failure of complete recovery after removal of procaine. The time parameters of recovery from procaine depression are independent of the previously applied concentrations of either acetylcholine or procaine. Since acetylcholine has been shown not to cross the nerve membrane, the results are interpreted as indicating that the receptor involved in the competition exists on the external surface of the membrane.

scholarly journals Feedback in the Contractile Mechanism of the Frog Heart

1972 ◽  
Vol 60 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Emil Bozler
Keyword(s):  
Low Temperatures ◽  
Time Course ◽  
Low Frequency ◽  
Feedback Mechanism ◽  
Frog Heart ◽  
Contractile Mechanism ◽  
Quick Release ◽  
Rapid Changes ◽  
Frog Ventricle ◽  
Rapid Drop

Shortening causes a transient decrease, extension an increase, in activity during contractures of the frog ventricle induced by high Ca or by isosmotic K solution. This is shown by the fact that, after the immediate passive shortening, the muscle is extended under isotonic conditions when the load is diminished, and that under isometric conditions quick release causes first a rapid drop, then a further, much slower, fall of tension. Increasing the load or stretching induce the opposite effects. At low temperatures all rapid changes in length produce oscillations of low frequency. These responses are due to a sensitive feedback mechanism similar to that previously demonstrated for insect fibrillar muscle. That this mechanism comes into play in the heart under normal conditions and controls the time-course of the twitch is demonstrated by the observation that relaxation begins earlier the greater the shortening. Thus, during afterloaded isotonic twitches the onset of relaxation is advanced as the load is diminished.

scholarly journals Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties

2021 ◽  
Vol 14 (8) ◽  
pp. 748
Author(s):  
Péter P. Nánási ◽  
Balázs Horváth ◽  
Fábián Tar ◽  
János Almássy ◽  
Norbert Szentandrássy ◽  
...  
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Laboratory Animals ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Human Cardiomyocytes ◽  
Ventricular Cells ◽  
Repolarization Reserve ◽  
Electrophysiological Studies ◽  
K Current

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

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