Negative inotropic effect of extracellular calcium buffering in cardiac muscle

1987 ◽  
Vol 252 (2) ◽  
pp. C248-C252 ◽  
Author(s):  
Y. Shimoni ◽  
S. Ginsburg
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Heart Muscle ◽  
Calcium Concentration ◽  
Negative Inotropic Effect ◽  
Intracellular Acidosis ◽  
Calcium Buffering ◽  
The Mean ◽  
Frog Atrium ◽  
External Calcium

Heart muscle contracts more vigorously when calcium levels are raised. A transient depletion of calcium from restricted extracellular spaces occurs with each contraction. We decided to maintain the concentration of this ion at a constant level by using an external calcium buffering system. It was found that buffering calcium at a millimolar level (using citrate as a buffer) caused a decrease, rather than an increase in the strength of contraction. The mean reduction in peak tension was by 27% in guinea pig and by 50.5% in frog atrium. This finding is analyzed; its most plausible explanation is the hypothesis that the buffer dissipates a calcium inhomogeneity, consisting of a higher calcium concentration adjacent to the membrane. Alternative interpretations such as intracellular acidosis, were tested experimentally and ruled out.

scholarly journals Propagation of Action Potentials and the Structure of the Nexus in Cardiac Muscle

1965 ◽  
Vol 48 (5) ◽  
pp. 797-823 ◽  
Author(s):  
L. Barr ◽  
M. M. Dewey ◽  
W. Berger
Keyword(s):  
Guinea Pig ◽  
Cardiac Muscle ◽  
Action Potentials ◽  
Structural Changes ◽  
Sucrose Solution ◽  
Electrical Coupling ◽  
Intercalated Discs ◽  
Sucrose Gap ◽  
Specialized Structure ◽  
Frog Atrium

The hypothesis that the nexus is a specialized structure allowing current flow between cell interiors is corroborated by concomitant structural changes of the nexus and changes of electrical coupling between cells due to soaking in solutions of abnormal tonicity. Fusiform frog atrial fibers are interconnected by nexuses. The nexuses, desmosomes, and regions of myofibrillar attachment of this muscle are not associated in a manner similar to intercalated discs of guinea pig cardiac muscle. Indeed, nexuses occur wherever cell membranes are closely apposed. Action potentials of frog atrial bundles detected extracellularly across a sucrose gap change from monophasic to diphasic when the gap is shunted by a resistor. This indicates that action potentials are transmitted across the gap when sufficient excitatory current is allowed to flow across the gap. When the sucrose solution in the gap is made hypertonic, propagation past the gap is blocked and the resistance between the cells in the gap increases. Electron micrographs demonstrate that the nexuses of frog atrium and guinea pig ventricle are ruptured by hypertonic solutions.

Effects of Ca2+ and catecholamines on the guinea pig atrium action potential plateau

1977 ◽  
Vol 233 (2) ◽  
pp. H203-H210
Author(s):  
R. B. Robinson ◽  
W. W. Sleator
Keyword(s):  
Guinea Pig ◽  
Calcium Concentration ◽  
Potassium Conductance ◽  
Slow Inward Current ◽  
Activation Process ◽  
Action Potential Plateau ◽  
Guinea Pig Atrium ◽  
Opposing Effects ◽  
Guinea Pig Atria ◽  
External Calcium

The activation process in isolated electrically driven guinea pig atria was studied by means of simultaneous microelectrode and tension recording. Reducing external calcium from 2.5 to 1.25 mM prolonged the plateau but further reduction of calcium shortened it. Progressively increasing doses of the calcium antagonist D600 (up to 1.4 micrometer), however, monotonically decreased plateau duration. Either protocol monotonically decreased steady-state tension, but with markedly different effects on the restitution relation. Epinephrine, and to a lesser extent isoproterenol, restored plateau duration after exposure to either a calcium-free or D600-containing solution, but only the isoproterenol effect was propranolol sensitive. Addition of calcium chelators enhanced rather than prevented the effect of epinephrine on plateau duration in a calcium-free solution, extending the plateau duration to more than 3 times normal in some cases. These results are explained in terms of two opposing effects of a change in calcium concentration on plateau formation, one action being through the slow inward current and the second through a shift in a calcium dependence of the inward-rectifying, potassium conductance system.

Effects of ouabain and calcium on potassium balance of isolated guinea pig ventricle

1962 ◽  
Vol 203 (6) ◽  
pp. 1130-1134 ◽  
Author(s):  
J. B. Kahn ◽  
Edwin Eakin ◽  
Don E. Levi
Keyword(s):  
Guinea Pig ◽  
Flow Rate ◽  
Binding Sites ◽  
Calcium Concentration ◽  
Ringer Solution ◽  
Potassium Balance ◽  
Anionic Binding Sites ◽  
External Calcium

Isolated guinea pig ventricles were perfused as follows: A—45 min with normal Krebs-Ringer solution containing tracer amounts of K42 (NKR*); B—15 min with NKR*, 15 min with KR* in which half the calcium was replaced with sodium (Ca/2-KR*), 15 min with NKR*; C—15 min with NKR*, 15 min with Ca/2-KR*, 15 min with Ca/2-KR* + 10–6 m ouabain; D—15 min with NKR*, 15 min with NKR* + 3.4 x 10–4 m pentobarbital (PB), 15 min with NKR* + PB + ouabain. K influx, net K loss, contraction height, and flow rate were determined, and K efflux was calculated. Decreasing the external calcium concentration ([Ca]e) decreased K efflux with no effect on K influx; restoring [Ca]e increased K efflux without affecting influx. Ouabain decreased K influx more than it decreased K efflux. If [Ca]e was constant, reducing the contraction height with PB did not affect K movements. These findings are consistent with the hypotheses that: 1) calcium and potassium can compete for fixed intracellular anionic binding sites and 2) calcium and ouabain produce their effects on K movements by different means.

Modulation of stimulation frequency responses and calcium dependency of functional parameters in hyperthyroid rat ventricular papillary muscles

1990 ◽  
Vol 68 (9) ◽  
pp. 1214-1220 ◽  
Author(s):  
E. K. Seppet ◽  
M. A. Eimre ◽  
A. P. Kallikorm
Keyword(s):  
Calcium Concentration ◽  
Contractile Function ◽  
Negative Inotropic Effect ◽  
Stimulation Frequency ◽  
Papillary Muscles ◽  
Time To Peak ◽  
Frequency Responses ◽  
Contractile Parameters ◽  
The Mean ◽  
Muscle Groups

The effects of stimulation frequency (0.2–1.5 Hz) and extracellular calcium concentration ([Ca2+]o) (0.6–15.0 mM) on the contractile function of thin papillary muscles of euthyroid and hyperthyroid rats were studied. Hyperthyroidism led to a decrease in developed tension (DT) and time to peak tension (TPT), but it exhibited no influence on the maximal rates of contraction (+dT/dt) and relaxation (−dT/dt). Also, the mean rates of contraction were similar in euthyroid and hyperthyroid muscle groups. The increase in stimulation frequency brought about a marked decrease in DT, +dT/dt, and −dT/dt of euthyroid papillary muscles at lower frequencies in comparison to papillary muscles in the hyperthyroid group. At stimulation frequencies above 1.0 Hz, the absolute and relative levels of DT and −dT/dt of hyperthyroid myocardium were elevated over euthyroid preparations. At the same time, TPT was unchanged in any of the muscle groups. Hyperthyroidism modulated the relationships between contractile parameters and [Ca2+]o. At a [Ca2+]o of 1.0–4.0 mM, the DT of hyperthyroid papillary muscles was lower than in euthyroid muscle. At 4.0 and 8.0 mM of [Ca2+]o, the equal values of maximal DT were registered for euthyroid and hyperthyroid papillary muscles, respectively. An increase in the [Ca2+]o in the range of 1.0–15.0 mM was accompanied by an increase in TPT of both muscle groups, but to a greater extent in hyperthyroid myocardium. In conclusion, the myocardium of hyperthyroid rat appeared to exhibit decreased sensitivity to calcium as well as to the negative inotropic effect of enhanced stimulation frequency. Alterations of the processes of transsarcolemmal movement and intracellular recycling of Ca2 may be implicated.Key words: euthyroid, hyperthyroid, myocardium, contractility, frequency, Ca2+ transport, sarcolemma, sarcoplasmic reticulum.

They effects of catecholamines on tension reactivation in cardiac muscle

1987 ◽  
Vol 231 (1263) ◽  
pp. 231-249 ◽  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Guinea Pig ◽  
Cardiac Muscle ◽  
Time Course ◽  
Calcium Currents ◽  
Short Intervals ◽  
Rat Atria ◽  
Reactivation Process ◽  
Guinea Pig Atria ◽  
Frog Atrium

The effects of adrenaline and the β-agonist isoprenaline on the time course of tension reactivation were studied in several cardiac tissues. The aim of the study was to assess whether experimental evidence can be found for a role of the sarcoplasmic reticulum in the reactivation of tension. It was assumed that calcium recycles between different parts of the reticulum, and that this recycling may affect tension repriming. Isoprenaline was assumed to enhance such recycling by increasing the uptake of calcium, following its release during a preceding contraction. Isoprenaline (in the range of 40 nM to 4 μM) was found to enhance tension repriming in adult guinea pig atria. However, in adult rat atria, isoprenaline often gave a complex effect, with a smaller degree of repriming at short intervals, and enhanced repriming at longer intervals. This was thought to reflect the balance between the enhancing effect of the drug on calcium recycling and an augmented release from the sarcoplasmic reticulum (SR). In striking contrast, there was no effect of isoprenaline on tension repriming in neonatal guinea pig atria and a retardation in neonatal rat atria. This was interpreted as reflecting the lack of a sarcoplasmic network in the neonatal tissue. The effects of isoprenaline on tension repriming in the frog atrium (which also has a sparse sarcoplasmic reticulum network) were also found to be complex; low concentrations (40 nM) enhanced the process, and high concentrations (0.4 μM) retarded it. Intermediate levels often produced a ‘crossover’ effect: more reacti­vation at short intervals, and less at long intervals. The interpretation of these results was that there are two processes which interact to determine the amount of tension produced at short intervals after each contraction: the basal reactivation process and some augmenting mechanism superimposed on it. This mechanism is probably related to other behavioural features of cardiac muscle, such as rate-dependent increases in membrane calcium currents. It is relevant mainly in those cases where tension repriming depends on membrane calcium currents. Further experiments (in the frog atrium) with elevated calcium and with the α-adrenergic agonist phenylephrine (both of which slowed down the reactivation process) also support this idea. These agents elevate internal calcium levels, and presumably saturate the augmenting mechanism (by producing maximal tension responses). By removing this mechanism, the apparent repriming time course is slower, because at each interval less tension can be generated in the absence of the contribution of the augmenting factor. It is not known to what extent such augmen­tation participates in determining tension in the adult mammalian heart, where a more complex interaction must exist between the sarcolemma and SR mechanisms.

Modulation of effect of extracellular calcium buffering in cardiac muscle

1989 ◽  
Vol 257 (6) ◽  
pp. H1843-H1850
Author(s):  
S. Ginsburg ◽  
Y. Shimoni
Keyword(s):  
Guinea Pig ◽  
Calcium Binding ◽  
Negative Inotropic Effect ◽  
Sodium Concentration ◽  
Extracellular Calcium ◽  
Calcium Currents ◽  
Inotropic Effect ◽  
Free Calcium ◽  
Intracellular Acidosis ◽  
Novel Approach

The buffering of extracellular calcium by citrate, with identical free calcium levels in the buffered and unbuffered medium, was previously found to markedly reduce tension in frog and guinea pig atria. We now report the following results. 1) In guinea pig, postest contractions are not reduced by citrate. 2) In frog the negative inotropic effect of citrate is greatly attenuated by partially replacing extracellular sodium concentration ([Na+]o) with lithium or sucrose. In contrast, in low [Na+]o, sodium salts of weak acids (which cause intracellular acidosis) still reduce tension. These findings strongly support the suggestion that citrate does not reduce tension directly, e.g., by causing intracellular acidosis or by reducing voltage-dependent calcium currents. 3) Higher stimulation rates also decrease the effect of citrate. 4) Treatment with neuraminidase or phospholipase D, both of which alter sarcolemmal calcium binding, dose not change the effect of citrate. 5) The positive inotropic effect of strophanthidin is reversibly lost in the presence of citrate. Our results provide a different, novel approach to support earlier suggestions that the extracellular matrix and/or the sarcolemma contain abundant calcium-binding sites that supply some of the calcium for contraction. Citrate presumably binds calcium more strongly, thereby "trapping" calcium released from the extracellular "stores," so that less calcium is made available for contraction. The inotropic effect of cardiac glycosides may also depend on the calcium that is bound to these stores.

scholarly journals Calcium uptake by mitochondria isolated from muskrat and guinea pig hearts

1991 ◽  
Vol 157 (1) ◽  
pp. 133-142
Author(s):  
T. A. McKean
Keyword(s):  
Guinea Pig ◽  
Calcium Concentration ◽  
Calcium Uptake ◽  
Membrane Damage ◽  
Indirect Measurements ◽  
45Ca Uptake ◽  
Hypoxia Ischemia ◽  
Interfibrillar Mitochondria ◽  
External Calcium

Subsarcolemmal and interfibrillar mitochondria were isolated from the hearts of the diving muskrat and non-diving guinea pig and direct and indirect measurements of calcium uptake were examined in vitro. The calcium-stimulated respiration rate and 45Ca uptake were measured and found to be greater in muskrat than in guinea pig mitochondria. Muskrat mitochondria were able to endure a greater external calcium concentration than guinea pig mitochondria before exhibiting indications of inner membrane damage. Calcium uptake by muskrat heart mitochondria was inhibited more by 1 mmoll-1 MgCl2 than was uptake by guinea pig mitochondria. No differences were detected between the interfibrillar and subsarcolemmal populations of mitochondria within species. An increased ability to sequester calcium by mitochondria without causing them damage may aid an animal during recovery from hypoxia, ischemia or acidosis.

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