Biomedical subjects

Y Shimoni

Publications and source records attributed to Y Shimoni.

At least 55 records · Page 3Linked to original sources

PubMed1992

Activin can generate ectopic axial structures in chick blastoderm explants.

We have recently shown that activin can induce the formation of axial structures from chick blastulae and that activin beta-B is transcribed, in the hypoblast of the chick, at the same stage that axial mesoderm is being induced. It was not clear, however, whether activin was merely allowing the central epiblastic cells to express a differentiated phenotype for which they were already prepared. This report shows that activin-containing medium (ACM) can act as an instructive inductor, which can change the fate of competent cells and bring about the formation of an ectopic embryonic axis. Furthermore, we show data that suggest that during normal development only one axis is obtained as a result of a carefully controlled inhibitory process.

Activins↗

PubMed1991

Loop diuretics block calcium currents in cardiac cells.

Loop diuretics are widely used drugs; serving to alleviate congestive heart failure and hypertension. Their mechanism of action is considered to be an inhibition of sodium retention in the kidneys, by a block of the Na/K/Cl cotransporter. The ensuing natriuresis and diuresis reduces blood pressure and alleviates congestive heart failure. Several earlier reports suggested direct cardiovascular effects, partly preceding the onset of diuresis. In the present study, evidence is presented for a direct action of two loop diuretic agents, bumetanide and furosemide, on cardiac L-type calcium currents in rabbit ventricular and atrial myocytes. This current is reversibly reduced by micromolar concentrations of these drugs. The onset of this effect can be observed within 1-2s, which could indicate a direct action on the calcium channel, independent of secondary effects subsequent to inhibition of the cotransporter. Thus, part of the therapeutic effects of the loop diuretics may be achieved through a direct reduction of cardiac output.

Animals↗

PubMed1991

Effects of aluminium on electrical and mechanical properties of frog atrial muscle.

1. The effects of aluminium on membrane ionic currents were studied in single cardiac myocytes. Most of the work was done on frog atrial cells, but some experiments were also carried out on single cells isolated from rabbit ventricles and atria. 2. The effects of aluminium on the force of contraction of frog atrial trabeculae were also investigated. 3. Aluminium was prepared from AlCl3 as a stock 0.5 M solution which has a pH of 3.5. Before each experiment, this solution was added to the control solution, to give a final concentration of 20-100 micrograms ml-1 aluminium (0.75-3.75 mM AlCl3). The solutions were brought to a pH of 7.4 or 7.6. at which they consist of a mixture of amorphous aluminium hydroxides and a very small amount of soluble ionic aluminium complexes: free aluminium cations (less than 10 pM), aluminohydroxide anions (less than 8 microM). The addition of this suspension reduced the peak inward calcium currents in single rabbit atrial and ventricular cells and in frog atrial cells. In the latter, the peak current was reduced (at + 10 mV) to 45% of control (mean of 9 cells). This effect was reversible upon washout, and was obtained at all membrane potentials, with no shift of the calcium current voltage relationship along the voltage axis. 4. Aluminium also reduced the time-dependent potassium current IK. This reduction was observed at all membrane potentials. For example, at + 10 mV, the mean reduction of IK (n = 9) was to 69% of the control amplitude. This effect, which was very difficult to reverse, was not due to IK rundown. The fully activated current-voltage relationships (obtained by standard 'tail' analysis) showed that the effect of aluminium was due mainly to a decrease in conductance and not to a shift in the activation range of IK. The mean voltage of half activation was shifted by 8 mV in the depolarizing direction (n = 5). 5. The background potassium current IK1 was also slightly but consistently changed in a complex fashion, with an outward shift at membrane potentials positive to -60 mV. For example, at a membrane potential of -40mV, the mean shift was by 22 + 4pA. At more negative potentials, there was an inward shift in the current amplitudes. For example, for steps to -I00 mV the current elicited was larger (more inward) by 53 pA (mean value, n = 10). The reversal potential was slightly shifted (<10 mV) in the hyperpolarizing direction. 6. The force of contraction of frog atrial trabeculae was altered by aluminium in a complex manner, which showed marked seasonal variation. During most of the year, 50-100,ug ml-1 aluminium caused a biphasic change, with an early small and consistent decrease, followed by a large increase in twitch amplitude. For a short period corresponding to the (local) winter months the sensitivity to aluminium was greatly enhanced. Aluminium lOOupgml-1 totally abolished contraction (n = 5), while a lower concentration (20,ug ml- 1) produced a sustained reduction in the force of contraction. Similar biphasic and seasonal responses have been reported to be induced by lanthanum. 7. The biphasic changes in twitch amplitude were independent of the transmembrane sodium gradient. Aluminium produced the same effects when 90% of the extracellular sodium was replaced by lithium. Caffeine (5 mM) attenuated or even inverted the positive inotropic effect of aluminium. These results imply that aluminium alters the release of calcium from intracellular, caffeine-sensitive stores. This could be effected either by augmenting the amount released during each activation, and/or by increasing the loading of stores prior to release.

Aluminum↗

PubMed1990

Activin can induce the formation of axial structures and is expressed in the hypoblast of the chick.

We show that PIF/activin can induce the formation of axial structures including a full-length notochord, segmented somites, and a neural tube in isolated epiblasts from chick blastulae. Using degenerate PCR primers, we have cloned a fragment of the activin beta B chain from chick hypoblast cDNA, and a fragment of the activin beta A chain from chick genomic DNA. Furthermore, we show that in the chick, activin is transcribed precisely when axial mesoderm is being induced. Since exogenous PIF/activin can induce the formation of axial structures and since activin beta B is transcribed at the time and place where the mesodermal axial structures are being induced, we propose that in the chick, activin B is the endogenous inducer of the body axis.

Activins↗

PubMed1990

Induction by soluble factors of organized axial structures in chick epiblasts.

Inductive action of soluble factors was tested on isolated chick epiblasts. An assay was developed wherein conditioned medium derived from the Xenopus XTC cell line induced the formation of a full-length notochord and rows of bilaterally symmetric somites. Basic fibroblast growth factor, epidermal growth factor, retinoic acid, and transforming growth factor type B1 and B2 were not capable of inducing axial structures. Thus, soluble factors can elicit the development of polarity stored in the epiblast and behave as true morphogens since they can induce the formation of the organized complex structures that constitute the embryonic axis.

Animals↗

PubMed1990

Pregnancy and complicated familial Mediterranean fever.

Familial Mediterranean Fever (FMF) is an inherited disease, closely following the pattern of autosomal recessive inheritance. Amyloidosis is the most severe complication of the disease. The prevalence of pregnancy loss in women with FMF is considered to be high. There is no information to support the possibility of increase risk of late pregnancy complications or change in the natural course of the disease. Two cases are presented with complicated FMF. One case with proved amyloidosis and the second patient with ascites. Pregnancy and neonatal outcome were uneventful in both. No further deterioration in the systemic disease occurred.

Adult↗

PubMed1990

Alpha-adrenergic modulation of the transient outward current in rabbit atrial myocytes.

1. A whole-cell voltage-clamp technique has been used to study the alpha-effects of the adrenergic agonists noradrenaline, methoxamine and phenylephrine on the action potentials and membrane currents of rabbit atrial myocytes. Experiments were carried out at 22-23 degrees C. 2. In the presence of 10(-6) M-propranolol, all three agents prolonged action potential duration. This change could be ascribed principally to changes in membrane current early during the plateau phase of the action potential. In the presence of 10(-3) M-4-aminopyridine, no changes in calcium current (ICa) were observed on exposure to alpha-agonists. No significant shift in the voltage dependence or change in the amplitude of the calcium current-voltage relation was observed. 3. Exposure to 3 x 10(-4) M-CdCl2 to block ICa reduced the action potential prolongation caused by alpha-adrenergic agonists. Measurement of unloaded cell shortening revealed that action potential prolongation caused by alpha-agonists, especially at low stimulus rates, could contribute significantly to the positive inotropic effect of alpha-adrenoceptor stimulation. 4. The voltage-activated transient outward current (It) was markedly reduced during exposure to alpha-adrenergic agonists in a dose-dependent manner in the presence of CdCl2 (3 x 10(-4) M) and propranolol in sufficient concentration to prevent beta-adrenoceptor activation. Noradrenaline exhibited a higher potency for this effect than either methoxamine or phenylephrine. The noradrenaline concentration required to give 50% of the maximal effect was 6 x 10(-6) M compared with 2.3 x 10(-4) M for methoxamine. Noradrenaline reduced It by only about 60% of the maximum reduction produced by methoxamine suggesting that it could be classified as a partial agonist for this effect. 5. The reduction of It during exposure to alpha-adrenergic agonists was rate dependent in that larger current reductions were observed at very low rates of stimulation (less than 0.1 Hz). 6. The magnitudes of current-voltage relations for It were reduced over the entire voltage range studied during exposure to alpha-adrenergic agonists and reductions were dose dependent. No shift of these relations along the voltage axis was observed. 7. The steady-state inactivation relations for It were studied using two voltage clamp protocols. A two-step method resulted in a relatively steep sigmoid 'quasi-steady-state' relation. The half-inactivation potential of -27 mV was unaffected by alpha-adrenergic agonists.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1989

Slow inward tail currents in rabbit cardiac cells.

1. A whole-cell gigaseal suction microelectrode voltage-clamp technique has been used to study slow inward tail currents in single myocytes obtained by enzymatic dispersion of rabbit ventricle and atrium. A variety of stimulation protocols, Tyrode solutions and pharmacological agents have been used to test three hypotheses: (a) that the slow inward tail current is generated by an electrogenic Na(+)-Ca2+ exchanger; (b) that a rise in [Ca2+]i, due to release from the sarcoplasmic reticulum can modulate the activity of this exchanger; and (c) that the uptake of calcium by the sarcoplasmic reticulum is a major determinant of the time course of the tail current. 2. As shown previously in amphibian atrium and guinea-pig ventricle, slow inward tail currents can be observed consistently under conditions in which action potentials and ionic currents are recorded using microelectrode constituents which only minimally disturb the intracellular milieu. 3. In ventricular cells, the envelope of these tail currents obtained by varying the duration of the preceding depolarizations shows that (a) the tail currents are activated by pulses as short as 10 ms, and reach a maximum for pulse durations of 100-200 ms, (b) the rate of decay of the tail current gradually increases as the activating depolarizations are prolonged, and (c) the tails cannot be due to deactivation of calcium currents, in agreement with other studies in frog heart. 4. When the mean level of [Ca2+]i is raised following inhibition of the Na(+)-K+ pump by strophanthidin (10(-5) M) or reductions in [K+]o (0.5 mM), the slow inward tail grows in size prior to the onset of a contracture or other signs of calcium-induced toxicity. 5. In a number of different preparations, replacement of [Ca2+]o with BaCl2 markedly or completely inhibits the Na(+)-Ca2+ exchanger, whereas Sr2+ replacement does not have this effect. In myocytes from rabbit ventricle the slow inward tails are reduced significantly and decay more slowly in 0.5-2.2 mM-BaCl2 Tyrode solution, while in 2.2 mM SrCl2 these tails are not altered. 6. The slow inward tail also shows a dependence on [K+]o, corresponding to previous data on Na(+)-Ca2+ exchange in other tissues. Increasing [K+]o in the Tyrode solution to a final concentration of 10-15 mM results in a marked inhibition of the slow tails. This effect cannot be accounted for by changes in the inwardly rectifying potassium current, IK1. 7. The slow tail currents were changed significantly by increasing the temperature of the superfusing Tyrode solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Comparison of sodium-calcium exchanger and transient inward currents in single cells from rabbit ventricle.

1. Whole-cell voltage-clamp measurements have been made in rabbit ventricular myocytes under conditions in which both Na(+)-Ca2+ exchanger currents (IEX, slow tails) and transient inward currents (ITI or TI) can be recorded. A number of experimental manoeuvres have been used in an attempt to separate or dissociate these two currents. 2. As expected, partial inhibition of the Na(+)-K+ pump by application of 0.54 mM [K+] Tyrode solution or 10(-5) M-strophanthidin induced TI currents which were recorded in the presence of IEX slow tails. 3. Complete inhibition of the Na(+)-K+ pump with zero [K+] Tyrode solution resulted in larger and more frequent TIs but smaller IEX tails. 4. A somewhat similar dissociation between ITI and IEX was observed when NaCl was reduced to 37.5 mM by using LiCl to replace NaCl. This inhibited the Na(+)-Ca2+ exchanger current, but induced ITI. 5. Transient inward currents and IEX tails could also be separated by selected patterns of stimulation (voltage-clamp depolarizations): following the second pulse of a pair of stimuli, IEX was significantly reduced whereas the TIs increased in size and frequency. 6. Additional experimental tests involving changes in external divalent ions could also separate these two currents. Increasing [Ca2+]o 3-fold increased the TIs without changing IEX. Shortly after [Ca2+]o was replaced with either [Ba2+]o or [Sr2+]o the TIs were blocked but IEX was unchanged. Application of MnCl2 (1 mM) and elevation of [K+]o inhibited IEX but did not significantly change the TI currents. 7. Application of caffeine (5-10 mM) or ryanodine (2 x 10(-6) M) blocked the TI currents at times when the IEX tails were not changed. 8. In combination these results suggest that even though both IEX and ITI are triggered (activated) by increases in [Ca2+]i, these two currents are distinct. IEX is generated by electrogenic Na(+)-Ca2+ exchange, while the TI currents may be due to Ca2(+)-activated cation-selective channels in the sarcolemma.

Animals↗

PubMed1989

A novel effect of norepinephrine on cardiac cells is mediated by alpha 1-adrenoceptors.

In the heart, alpha-adrenergic agonists have long been known to produce a positive inotropic effect that is rate dependent and associated with action potential prolongation but is not accompanied by adenosine 3',5'-cyclic monophosphate (cAMP) elevation. The ionic mechanism of these effects is unknown. We report that a transient outward K+ current, a major determinant of plateau duration in rabbit and human atria, is strongly inhibited by norepinephrine and the alpha-adrenoceptor agonists methoxamine and phenylephrine. These effects of alpha-stimulation can be blocked by prazosin. The reduction in the transient outward current substantially slows action potential repolarization. These results can explain the regional and species-dependent positive inotropic effects of alpha-adrenergic stimulation in the heart and give important new insight into the autonomic regulation of cardiac function. In addition, reduction in this repolarizing current during the enhanced alpha-adrenergic responsiveness of myocardial ischemia may be a factor in the genesis of arrhythmias produced by catecholamines.

Adrenergic alpha-Agonists↗

PubMed1989

Modulation of effect of extracellular calcium buffering in cardiac muscle.

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.

Animals↗

PubMed1989

Retinoic acid inhibits growth in agarose of early chick embryonic cells and may be involved in regulation of axis formation.

The mechanisms involved in the generation of axial structures in the chick are well documented, yet, little is known about the actual factors that generate such a complex pattern. The recent demonstrations that all-trans-retinoic acid (RA) acts as a morphogen during limb development (Thaller and Eichele, 1987) lead us to examine whether during axis formation in the developing chick, RA could be one of the factors involved. We now show that retinoic acid can block a very unusual property of normal early chick embryonic cells, mainly their capacity to grow in semisolid medium. We also present experiments that suggest that RA may play a direct role during axis formation in the developing chick.

Animals↗

PubMed1988

Tension reactivation and potentiation in guinea pig atrium: the effects of isoprenaline, calcium and rate changes.

The process of tension repriming and the phenomenon of tension potentiation after premature stimulation (post-extrasystolic potentiation, PESP) were studied in the adult guinea pig atrium. The following results were obtained. (i) Reducing extracellular calcium, [Ca]o, to 50% of normal did not significantly change the rate of tension repriming. However, in the presence of 5 microM isoprenaline (which greatly speeded up repriming) the same reduction in [Ca]o slowed down the repriming process. (ii) Increases in the rate of stimulation enhanced the rate of tension repriming in a control medium, but this rate-dependence was absent in the presence of isoprenaline. (iii) Isoprenaline (20 microM) abolished PESP. A reduction in [Ca]o or the addition of verapamil (still with isoprenaline) partly restored tension potentiation. In neonatal guinea pig atria, a large PESP was evident, which was only slightly reduced by isoprenaline. These results are interpreted as reflecting changes induced by isoprenaline in the degree of filling of sarcoplasmic reticulum (SR) stores with calcium, and in the rate of calcium recycling between uptake and release sites within the SR network. The large PESP found in the neonate, and its relative insensitivity to isoprenaline was interpreted as reflecting a scarcity of SR. This implies that tension potentiation may also reflect changes in sarcolemmal calcium currents.

Animals↗

PubMed1988

The effects of prenylamine on single ventricular myocytes of guinea-pig.

1. The action of prenylamine, an antianginal drug, was studied in single ventricular guinea-pig myocytes. In concentrations of 10-50 microM, prenylamine significantly (P less than 0.01) shortened action potentials, and significantly (P less than 0.001) reduced the inward calcium current by 29% to 76% (n = 7). This effect was also present in the presence of adrenoceptor-blockade (with phentolamine and propranolol), and was thus not due to indirect changes in endogenous catecholamine action. 2. Prenylamine did not affect the steady state level of current at the end of long pulses, and does therefore not act by changing time-dependent outward currents. Since the resting potential in the unclamped mode is unchanged during gross changes in action potential duration, it is also unlikely that there are any changes in the background, time-independent potassium conductance. 3. It is concluded that prenylamine has a direct effect on cardiac calcium channels, not mediated by adrenoceptor activation.

Animals↗

PubMed1987

The effects of catecholamines on tension reactivation in cardiac muscle.

The effects of adrenaline and the beta-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 microM) 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 microM) 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 alpha-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).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

The control of calcium current reactivation by catecholamines and acetylcholine in single guinea-pig ventricular myocytes.

The time course of reactivation of the calcium current in isolated single cardiac cells is complex. The rising phase is sigmoid and there is an overshoot. Catecholamines increase the initial rate of reactivation but reduce or abolish the overshoot. This combination of effects results in a 'crossover', so that the net effect of adrenaline depends on the pulse interval used. Acetylcholine not only reduces the current amplitude, it also substantially slows recovery. At short intervals the effect of acetylcholine is therefore very large. Agents that increase intracellular cyclic AMP levels affect the amplitude of the current but do not have a large effect on the reactivation time course. It is suggested that the autonomic transmitters exert their effects by controlling the local calcium concentration near the inner surface of the channels. This is supported by the fact that there are natural variations in reactivation time course between different cells and that these are correlated with their calcium loading, as judged by other electrophysiological criteria, such as the speed of calcium current inactivation and the presence of the calcium-dependent slow inward current.

Acetylcholine↗

PubMed1987

Inward current related to contraction in guinea-pig ventricular myocytes.

1. A component of inward current has been identified in isolated guinea-pig ventricular cells that is closely correlated with the contraction of the cell and not with the rapidly activated calcium current. This is a delayed current most clearly seen as a current 'tail' after 50-200 ms depolarizing pulses. At 22 degrees C the delayed current has a maximum amplitude of approximately 0.5 nA at -40 mV (consistently 10-20% of the peak amplitude of the calcium current) and decays with a half time of approximately 150 ms. 2. Paired-pulse protocols show that at pulse intervals (300-400 ms) at which the calcium current is nearly fully reprimed, the delayed component is very small. It recovers over a time course of several seconds, as does the contraction. Adrenaline speeds the decay of the delayed current (approximately 50%) and similarly accelerates cell relaxation. Adrenaline also shortens the recovery time of both the contraction and the delayed current. 3. During long trains of repetitive pulses, the delayed current amplitude follows that of the contraction 'staircase'. The half-time of the decay of the current 'tail' also matches that of contraction and suggests that both may reflect the time course of the underlying intracellular calcium transient. 4. The half-time of decay of the delayed current is only moderately voltage dependent over the potential range -80 to 0 mV. The amplitude of the delayed current normally reaches a minimum around -20 mV and increases at more negative potentials. 5. The voltage dependence and kinetics of decay of the current show that it should flow and decay largely during the action potential plateau and repolarization rather than during diastole. 6. Diffusion of high concentrations of EGTA into cells abolishes the delayed current and cell contraction. Under these conditions the fast calcium current is increased and its inactivation delayed. 7. When calcium is replaced by strontium, the delayed current amplitude is greatly reduced even though the contraction is larger and slower. 8. The results are consistent with the hypothesis that the delayed inward current is activated by the intracellular calcium transient. It may be carried by the sodium-calcium exchange process and/or by calcium-activated non-specific channels (especially when interal calcium is elevated by reduction of external sodium). 9. In the presence of 1 microM-ryanodine, the calcium current is greatly reduced, whereas the delayed current is not significantly altered.

Action Potentials↗

PubMed1987

Physiological changes induced in cardiac myocytes by cytotoxic T lymphocytes.

The "lethal hit" induced by viral specific, sensitized, cytotoxic T lymphocytes (CTL) attacking virus-infected heart cells is important in the pathogenesis of viral myocarditis and reflects the key role of CTL in this immune response. The mechanisms involved are incompletely understood. Studies of the physiological changes induced in mengovirus-infected, cultured, neonatal, rat heart cells by CTL that had been previously sensitized by the same virus are presented. The CTL were obtained from spleens of mengovirus-infected, major histocompatibility complex (MHC) matched adult rats. Cell wall motion was measured by an optical method, action potentials with intracellular microelectrodes, and total exchangeable calcium content by 45Ca tracer measurements after loading the myocytes with 45Ca and then exposing them to CTL. After 50 min (mean time) of exposing mengovirus-infected myocytes to the CTL, the mechanical relaxation of the myocyte was slowed, with a subsequent slowing of beating rate and a reduced amplitude of contraction. Impaired relaxation progressed, and prolonged oscillatory contractions lasting up to several seconds appeared, with accompanying oscillations in the prolonged plateau phase of the action potentials. Arrest of the myocyte contractions appeared 98 min (mean time) after exposure to CTL. These changes in action potentials and contractions were reversible either by washout with the normal medium or by the addition of verapamil. The amount of total exchangeable calcium in the cultured myocytes, 1 h after exposure to CTL, was significantly increased. This increase was prevented by pretreatment with verapamil. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗