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Cheng-I Lin

Publications and source records attributed to Cheng-I Lin.

17 recordsLinked to original sources
PubMed2004

Effects of cyclopiazonic acid on triggered activities in ventricular muscle and cardiomyocytes isolated from hamster hearts.

The present experiments were performed to study the actions of cyclopiazonic acid on triggered activities generated in vitro in ventricular papillary muscle and cardiomyocytes isolated from the hearts of healthy male Syrian hamsters (Biobreeders F1B). Action potentials (APs) of ventricular muscle with a diameter around 1.5 mm were recorded using a microelectrode technique and force was recorded using a transducer. Ventricular preparations were driven at 2 Hz in high [Ca]o (9 mM)-low [K]o (1 mM) solution to induce delayed after depolarizations (DADs). Triggered activities were induced on resumption of electrical stimulation after a rest period of 20 sec. Effects of cyclopiazonic acid (3-10 microM) on steady-state rhythms and post-rest triggered activities were determined. Results revealed that cyclopiazonic acid initially enhanced the amplitude of DADs and induced post-rest triggered rhythms. However, after several minutes of cyclopiazonic acid exposure, AP duration (APD) was prolonged and DADs were significantly depressed. The effects on APD and DADs were reversible after washout of cyclopiazonic acid, but the diastolic potential during rest period oscillated and was able to generate high-frequency spontaneous APs at a reduced potential level. In ventricular myocytes isolated enzymatically, ionic currents were measured using of whole-cell patch-clamp techniques. In a high [Ca]o-low [K]o solution, a series of oscillatory transient inward currents (I(ti)) were obtained on repolarization to the holding potential (-45 mV) after a depolarizing pulse to the test potential of +20 mV for 1.2 sec. Cyclopiazonic acid (10 microM) reduced significantly the magnitude of I(ti). The present results in hamster ventricular cells suggested that cyclopiazonic acid by inhibiting the sarcoplasmic reticulum (SR)-Ca2+ pump would gradually deplete the amount of Ca2+ within the SR. The consequent reduction in the amount of Ca2+ released into the cytoplasm by cyclopiazonic acid might inhibit triggered arrhythmia through a reduction of DADs and I(ti).

Action Potentials↗
PubMed2004

Effect of ethanol on the electrophysiological characteristics of pulmonary vein cardiomyocytes.

Ethanol consumption has been considered to contribute to the occurrences of paroxysmal atrial fibrillation. Pulmonary veins are known to initiate atrial fibrillation. This study investigated whether ethanol may induce atrial fibrillation through increasing arrhythmogenic activity of pulmonary vein cardiomyocytes. Using the whole-cell clamp technique, the action potential and ionic currents were investigated in rabbit single pulmonary vein beating cardiomyocytes with and without (control) incubation of ethanol. Compared with control cardiomyocytes, pulmonary vein cardiomyocytes receiving 0.3 mg/ml or 1 mg/ml ethanol had shorter action potential duration, but had similar beating rates (2.6+/-1.3, 2.7+/-1.2, 2.7+/-1.2 Hz) and incidences (45%, 41%, 32%) of delayed after depolarization. Pulmonary vein cardiomyocytes receiving ethanol had smaller L-type Ca(2+) currents and larger transient outward currents, but had similar transient inward, delayed rectified outward, inward rectified and pacemaker currents. These results suggest that ethanol has no direct effect on the arrhythmogenic potential of pulmonary vein cardiomyocytes.

Action Potentials↗
PubMed2004

Electromechanical properties of Purkinje fiber strands isolated from human ventricular endocardium.

BACKGROUND: Abnormalities in the regulation of intracellular Ca2+ were observed in cardiac cells obtained from failing human hearts. However, the electromechanical properties and pharmacologic responses of human ventricular Purkinje fibers have not been well characterized. METHODS: Strands of free-running Purkinje fibers and/or trabecular muscle fibers with a diameter of around 1.5 mm were removed from the endocardial surface of ventricles obtained from 16 transplant recipient hearts. Action potential (AP) was detected by conventional microelectrode techniques and twitch force by a force-displacement transducer. RESULTS: The human Purkinje fiber strands as revealed by histologic examination were composed of Purkinje cells and the surrounding ventricular muscle cells. In well-polarized Purkinje fibers (mean +/- SE of maximum diastolic potential [MDP] = -85 +/- 1 mV) showing fast-response AP (Phase 0 Vmax >100 V/sec), the cardiotonic agents isoproterenol and strophanthidin (1 to 2 micromol/liter) accelerated the slope of diastolic depolarization and induced delayed afterdepolarization but not spontaneous APs. Steady-state contraction and the post-rest potentiation of contraction (PRPC) were similar in both Purkinje fibers and ventricular muscles, but inotropic agents induced tachyarrhythmia only in Purkinje fibers. In partially depolarized Purkinje fibers (MDP <-70 mV) with slow-response AP, isoproterenol and/or strophanthidin readily induced automatic and triggered rhythms. CONCLUSIONS: Accumulation of excessive cytosolic Ca2+ in the presence of cardiotonic agents could lead to tachyarrhythmias in Purkinje fibers, but rarely in ventricular muscles of failing human hearts.

Adult↗
PubMed2004

T-type calcium current in electrical activity of cardiomyocytes isolated from rabbit pulmonary vein.

INTRODUCTION: Pulmonary veins (PVs) are known to initiate paroxysmal atrial fibrillation. T-type calcium current (I(Ca-T)) has a role in normal and abnormal automaticity of cardiomyocytes. The aim of this study was to evaluate whether I(Ca-T) contributes to PV electrical activity. METHODS AND RESULTS: By whole-cell clamp techniques in rabbit myocytes, I(Ca-T) was identified in 12 (39%) of 31 PV cardiomyocytes with pacemaker activity, 2 (9%) of 23 PV cardiomyocytes without pacemaker activity, and 2 (15%) of 13 atrial myocytes (P < 0.05). Maximum I(Ca-L) and I(Ca-T) densities from PV cardiomyocytes with pacemaker activity were 6.87 +/- 2.17 pA/pF and 1.38 +/- 0.69 pA/pF, respectively. Nickel (40 microM) decreased the spontaneous activity in 5 (36%) of 14 PV cardiomyocytes (3.1 +/- 0.6 Hz vs 2.2 +/- 0.5 Hz, P < 0.05), reduced the amplitudes of delayed after depolarization from 13 +/- 1 mV to 7 +/- 1 mV (n = 4, P < 0.05) and inhibited transient inward currents from 1.2 +/- 0.2 pA/pF to 0.7 +/- 0.1 pA/pF (n = 11, P < 0.01). CONCLUSIONS: We conclude that I(Ca-T) contributes to PV pacemaker activity and triggered activity, which are of functional importance in PV arrhythmogenesis.

Action Potentials↗
PubMed2004

Oscillatory transient inward currents in ventricular myocytes of healthy versus myopathic Syrian hamster.

The present experiments were performed in order to study abnormal action potential configuration and ion channel activity in ventricular myocytes obtained from 23 male myopathic Syrian hamsters (Biobreeders strain 14.6, 32-52 weeks old) compared with 10 age-matched healthy control hamsters (Biobreeders F1B) by means of whole-cell patch-clamp techniques. The results show that the myopathic myocytes had a longer action potential duration, a reduced transient outward K(+) current on depolarization and a smaller transient inward current on repolarization after prolonged depolarizing pulses (> 500 msec). However, the L-type Ca(2+) current and the inwardly rectifing K(+) current were not significantly different from those of healthy myocytes. The oscillatory transient inward currents could be diminished by treatment with ryanodine (0.01-1 micromol/L), a sarcoplasmic reticulum (SR) Ca(2+) release channel blocker, or with Na(+)-free superfusate. We conclude that the hereditary myopathic hamsters are less likely to develop delayed after depolarization-related transient inward currents and triggered arrhythmias owing to a smaller SR Ca(2+) content.

Action Potentials↗
PubMed2003

Role of the sarcoplasmic reticulum in altered action potential and contraction of myopathic human and hamster ventricle.

1. The present experiments were performed in order to study the role of the sarcoplasmic reticulum (SR) in the altered action potential and contraction of ventricular myocardium obtained from myopathic Syrian hamster and explanted human hearts (n = 8). The hamsters included age-matched healthy hamsters (F1B; n = 18), young myopathic hamsters (Bio 14.6; n = 8; aged 17-27 weeks) and older myopathic hamsters (n = 10; aged 39-43 weeks). 2. Action potentials were recorded by means of a microelectrode technique and force was recorded using a transducer. Post-rest potentiation of contraction (PRPC), a measure of the SR Ca2+-pumping activity, was determined after different rest intervals (2-60 s). Furthermore, cyclopiazonic acid (10 micro mol/L), a specific blocker of SR Ca2+-ATPase, was used to unmask abnormalities in the function of the SR. 3. The relationship between PRPC and rest interval was similar in younger healthy and myopathic hamsters, but the curve of the older myopathic muscle was obviously shifted downwards. Cyclopiazonic acid decreased predominantly the ascending part of the curve in both the healthy and myopathic hamster myocardium and could induce spontaneous action potentials during drug exposure or after washout. 4. In human myopathic myocardium, the curve of the PRPC-rest interval peaked at longer intervals (40-60 s) compared with that of the hamsters (10-20 s). Cyclopiazonic acid markedly depressed the relationship and increased the diastolic force (contracture) at high driving frequency, but did not induce action potentials during the rest interval. 5. We conclude that an impaired function of the SR contributes to the progressive deterioration of ventricular function in dilated cardiomyopathy and that the electromechanical behaviour of the ventricular myocardium of patients affected by dilated cardiomyopathy shows similarity and differences with the myopathic Syrian hamster model.

Action Potentials↗
PubMed2003

Pathophysiology of the pulmonary vein as an atrial fibrillation initiator.

The basic electrophysiologic studies have proved the arrhythmogenic mechanisms of the pulmonary vein as an atrial fibrillation initiator; the mechanisms include enhanced automaticity, triggered activity, and microreentry from myocardial sleeves inside pulmonary veins. Immunohistology study has proved the conduction characteristics of pulmonary vein myocardium, and further study of ionic currents are important for understanding atrial fibrillation initiation from the pulmonary vein.

Animals↗
PubMed2003

Differential expression of connexin43 gap junctions in cardiomyocytes isolated from canine thoracic veins.

We investigated the phenotypic features of cardiomyocytes, including the gap junctions, in the myocardial sleeve of thoracic veins. Single cardiomyocytes, isolated from the canine pulmonary veins (PV) and superior vena cava (SVC) using digestive enzymes, were examined by immunoconfocal microscopy using antisera against connexin43 (Cx43), Cx40, and other cell markers. The results showed that isolated cardiomyocytes displayed rod shapes of various sizes, ranging from <50 microm to >200 microm in length, and all the cells expressed alpha-actinin and vinculin. Gap junctions made of various amounts of Cx43 and Cx40 were found at the cell borders. These two connexins were extensively co-localized. Comparison between the thoracic veins showed that cells of the SVC contained more Cx43 gap junctions (total Cx43 gap junctions area per cell surface area, 4.0 +/- 0.2% vs 1.5 +/- 0.2%; p<0.01). In addition, for single-nucleus cells, those from the PV were longer (103.7 +/- 3.6 vs 85.0 +/- 3.1 microm; p<0.01) but narrower (14.4 +/- 0.5 vs 16.9 +/- 0.9 microm; p<0.01). In conclusion, canine thoracic veins contain cardiomyocytes with differences in shape and gap junctions, suggesting that the electrical conduction properties may be different between the thoracic veins.

Animals↗
PubMed2003

Possible underlying mechanism for hydrogen peroxide-induced electromechanical suppression in human atrial myocardium.

Hydrogen peroxide (H(2)O(2)) and its metabolites have been shown to exert complex effects on the cardiac muscle during cardiac ischemia/reperfusion. The aim of the present study, by perfusing H(2)O(2) or/and different scavengers of oxygen free radicals (OFRs) into the human atrium, is to characterize the electropharmacological effects of H(2)O(2) and explore its possible underlying mechanism. Atrial tissues obtained from the heart of 19 patients undergoing corrective cardiac surgery were used. Transmembrane action potentials were recorded using the conventional microelectrode technique, and contraction of atrial fibers was evaluated in normal [K](o) (4 mM) in the absence and presence of tested agents. H(2)O(2) (30 micro M-3 mM) had a biphasic effect on the contractile force (an increase, followed by a decrease), reduced the 0-phase depolarizing slope (dV/dt), and prolonged the action potential duration (APD) in a concentration-dependent manner. However, even at a concentration as high as 3 mM, H(2)O(2) did not influence diastolic membrane potential (DMP). Pretreatment with N-(mercaptopropionyl)-glycine (N-MPG), a specific scavenger of the. OH free radical, significantly blocked the 3 mM H(2)O(2)-induced electromechanical changes, while the pretreatment with L-methionine (L-M), a specific scavenger of HOCl free radical, did not. Our data suggests that the toxic effects of H(2)O(2) are caused mainly through the generation of. OH, which is attributed to the electropharmacological inhibitory effects seen in the human atrium.

Adult↗
PubMed2002

Electrophysiology and arrhythmogenic activity of single cardiomyocytes from canine superior vena cava.

BACKGROUND: The superior vena cava (SVC) has been proved to be a focal point in the initiation of paroxysmal atrial fibrillation. The autonomic nervous system plays an important role in the genesis of atrial fibrillation. However, the arrhythmogenic potentials of SVC and its responses to autonomic agents are not clear. The purpose of this study was to isolate single SVC cardiomyocytes and to investigate their electrophysiological characteristics, as well as the direct effects of autonomic agents. METHODS AND RESULTS: Canine SVC cardiomyocytes were isolated by perfusion with digestive enzymes. The action potentials and ionic currents were investigated in single SVC cardiomyocytes using the whole-cell clamp technique. Dissociation of the SVC yielded rod-shaped single cardiomyocytes with (n=74, 51%) or without (n=71, 49%) pacemaker activities. There were similar densities of inward Ca2+, delayed rectifier K+, transient inward, inward rectifier K+, and pacemaker currents between SVC cardiomyocytes with and without pacemaker activity. SVC cardiomyocytes with pacemaker activity have, however, greater transient outward currents than those without pacemaker activity. In SVC cardiomyocytes, acetylcholine (5.5 micromol/L) abolished the spontaneous activities, but isoproterenol (10 nmol/L), atropine (10 micromol/L), and phenylephrine (10 micromol/L) accelerated the spontaneous activity and induced the occurrences of early or delayed afterdepolarizations. CONCLUSIONS: These findings suggest that SVC cardiomyocytes have distinct action potentials and ionic current profiles that may be responsible for the arrhythmogenic activity of the SVC.

Action Potentials↗
PubMed2002

Hydrogen peroxide-induced intracellular acidosis and electromechanical inhibition in the diseased human ventricular myocardium.

Accumulation of oxygen free radicals is an important mediator of post-ischemia/reperfusion cardiac dysfunction. However, oxidative injury has not been well characterized in human cardiac tissues. In the present study, we superfused hydrogen peroxide (H(2)O(2)) into the diseased human ventricle in order to assess the effects of oxygen free radicals on the electromechanical parameters and the intracellular pH (pH(i)), and to test the ability of certain potential cardioprotective agents, including scavengers of hydrogen peroxide (dibenzamidostilbene disulfonic acid; DBDS), the.OH free radical (N-(mercaptopropionyl)-glycine; N-MPG), and the HOCl free radical (L-methionine), to protect against oxidative injury. Disease human ventricular tissues were obtained from patients undergoing heart transplantation. Electrophysiological experiments were performed using a traditional micropipette, while the pH(i) was measured by microspectrofluorimetry. We found that (a) H(2)O(2) (30 microM-3 mM) induced a significant dose-dependent intracellular acidosis, (b) H(2)O(2) (30 microM-3 mM) had a notable dose-dependent biphasic effect on the contractile force (an increase, followed by a decrease), while moderate concentrations of H(2)O(2) also inhibited the generation of action potential and increased the diastolic resting force significantly, and (c) N-MPG caused significant block of both the intracellular acidosis and the electromechanical inhibition induced by 3 mM H(2)O(2), whereas L-methionine and DBDS did not. Our data suggest that the toxic effects of H(2)O(2) are caused mainly through the generation of.OH, which is attributed to the intracellular acidosis seen in the diseased human ventricle.

Acidosis↗
PubMed2002

Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes.

OBJECTIVES: This study was conducted to investigate the effects of thyroid hormone on the electrophysiological characteristics of pulmonary vein (PV) cardiomyocytes. BACKGROUND: Hyperthyroidism is an important etiology of paroxysmal atrial fibrillation (AF). Pulmonary veins are known to initiate paroxysmal AF. METHODS: The action potential and ionic currents were investigated in single rabbit PV and atrial cardiomyocytes with (hyperthyroid) and without (control) incubation of L-triiodothyronine using the whole-cell clamp technique. RESULTS: Compared with the control cardiomyocytes, hyperthyroid PV and atrial cardiomyocytes had shorter action potential duration. Hyperthyroid PV cardiomyocytes had faster beating rates (1.82 +/- 0.13 Hz vs. 1.03 +/- 0.15 Hz, p < 0.005) and a higher incidence of delayed after depolarization (beating: 92% vs. 6%, p < 0.0001; non-beating: 45% vs. 3%, p < 0.005). However, only hyperthyroid PV beating cardiomyocytes had a higher incidence of early after depolarization (46% vs. 0%, p < 0.0001). The ionic current experiments showed that hyperthyroid PV beating cardiomyocytes had larger densities of overall slow inward (2.72 +/- 0.21 pA/pF vs. 2.07 +/- 0.19 pA/pF, p < 0.05), overall transient outward (1.39 +/- 0.21 pA/pF vs. 0.48 +/- 0.08 pA/pF, p < 0.001) and steady state outward currents (0.78 +/- 0.06 pA/pF vs. 0.58 +/- 0.04 pA/pF, p < 0.05) on depolarization and larger transient inward (0.021 +/- 0.004 pA/pF vs. 0.005 +/- 0.001 pA/pF, p < 0.001) on repolarization. By contrast, the hyperthyroid PV non-beating cardiomyocytes had larger densities of overall transient outward (1.01 +/- 0.14 pA/pF vs. 0.37 +/- 0.07 pA/pF, p < 0.001), steady state outward (0.61 +/- 0.06 pA/pF vs. 0.44 +/- 0.04 pA/pF, p < 0.05) and transient inward currents (0.011 +/- 0.002 pA/pF vs. 0.003 +/- 0.001 pA/pF, p < 0.05). CONCLUSIONS: Thyroid hormone changes the electrophysiological activity of the PV cardiomyocytes. Increased automaticity and enhanced triggered activity may increase the arrhythmogenic activity of PVs in hyperthyroidism.

Action Potentials↗
PubMed2002

Electrophysiology of single cardiomyocytes isolated from rabbit pulmonary veins: implication in initiation of focal atrial fibrillation.

Pulmonary veins (PVs) are important foci in initiation of paroxysmal atrial fibrillation. However, the mechanisms of the high arrhythmogenic activity of PVs are unclear. This study aimed to isolate single cardiomyocytes from PVs and evaluate their electrophysiological characteristics and arrhythmogenic potential. Cardiomyocytes of rabbit PVs were isolated by retrograde perfusion with digestive enzymes from aorta via left ventricle and left atrium. The action potentials and ionic currents were investigated in isolated single PV cardiomyocytes using the whole-cell clamp technique. Dissociation of PVs yielded single pacemaker cardiomyocytes (76%) and non-pacemaker cardiomyocytes with a fast response action potential. Both the pacemaker and non-pacemaker cardiomyocytes had similar inward Ca2+ currents and transient outward K+ currents. However, the pacemaker cardiomyocytes had a smaller inward rectifier K+ current (1.50 +/- 0.22 versus 4.21 +/- 1.15 pA/pF, P < 0.005) and a larger delayed rectifier K+ current (0.60 +/- 0.05 versus 0.24 +/- 0.05 pA/pF, P < 0.005) than non-pacemaker cardiomyocytes. Acetylcholine induced hyperpolarization and inhibited the spontaneous action potential. Isoproterenol (10 nM) accelerated the spontaneous activity and induced early or delayed afterdepolarization, which could be suppressed by nifedipine. The PV cardiomyocytes with early afterdepolarization have a greater prolongation of action potential duration (deltaAPD, +67 +/- 17 versus -109 +/- 20 ms, P < 0.0001) and a greater increase of inward Ca2+ current (0.90 +/- 0.23 versus 0.38 +/- 0.08 pA/pF, P < 0.05) after isoproterenol than those with out early afterdepolarization. These findings suggest that PV cardiomyocytes have distinct action potentials and ionic current profiles, which may be responsible for the high arrhythmogenic activity of the PVs.

Acetylcholine↗
PubMed2002

Functional evidence for intracellular acid extruders in human ventricular myocardium.

Intracellular pH (pH(i)) is a major homeostatic system within the cell. Changes in pH(i) exert great influence on cardiac contractility and rhythm. Both the housekeeping Na+ - H+ exchanger (NHE) and the Na+ - HCO3- symporter (NHS) have been confirmed as major transporters for the active acid extrusion mechanism in animal cardiomyocytes. However, whether the NHE and NHS functionally coexist in human ventricular cardiomyocytes remains unclear. We therefore examined the mechanism of pH(i) recovery following an NH4Cl-induced intracellular acidosis in the human ventricular myocardium. The pH(i) was monitored by microspectrofluorimetry by the use of intracellular 2',7'-bis(2-carboxyethyl)-5(6)-carboxy-fluorescein (BCECF)-fluorescence. HOE 694 (30 microM), a specific NHE inhibitor could block pH(i) recovery from induced intracellular acidosis completely in nominally HCO3- -free HEPES Tyrode solution, but it only partially inhibited the pH(i) recovery in 5% CO2/HCO3- Tyrode solution. In 5% CO2/HCO3- Tyrode solution, the addition of HOE 694 together with DIDS (an NHS inhibitor) or the removal of [Na+](o) could entirely inhibit the acid extrusion. We conclude for the first time that two different acid extruders, HCO3- -independent and -dependent, were most likely the NHE and NHS, respectively, that functionally coexisted in the human ventricular cardiomyocytes.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMedDate not supplied

Temperature regulates the arrhythmogenic activity of pulmonary vein cardiomyocytes.

Temperature plays an important role in the electrophysiology of cardiomyocytes. Pulmonary veins (PVs) are known to initiate paroxysmal atrial fibrillation. The effects of temperature on the arrhythmogenic activity of rabbit single PV and atrial cardiomyocytes were assessed using the whole-cell clamp technique. PV cardiomyocytes had different beating rates at low (22-25 degrees C), normal (38-39 degrees C) and high (40-41 degrees C) temperatures (0.9 +/- 0.1, 3.2 +/- 0.4, 6.4 +/- 0.6 Hz, respectively; p < 0.001). There were different action potential durations and incidences of delayed afterdepolarization in PV cardiomyocytes with pacemaker activity (31, 59, 63%; p < 0.05), PV cardiomyocytes without pacemaker activity (16, 47, 60%; p < 0.001), and atrial myocytes (0, 0, 21%; p < 0.05). However, oscillatory afterpotentials were only found in PV cardiomyocytes with pacemaker activity at normal (50%) or high (68%) temperatures, but not at low temperatures (p < 0.001). Both PV and atrial cardiomyocytes had larger transient inward currents and inward rectified currents at high temperatures. Additionally, PV cardiomyocytes with and without pacemaker activity had larger pacemaker currents at higher temperatures. This study demonstrated that PV cardiomyocytes have an increase in arrhythmogenic activity at high temperatures because of enhanced automaticity, induced triggered activity, or shortening of action potential duration.

Action Potentials↗
PubMedDate not supplied

Calcium overload and cardiac function.

The changes in cardiac function caused by calcium overload are reviewed. Intracellular Ca(2+) may increase in different structures [e.g. sarcoplasmic reticulum (SR), cytoplasm and mitochondria] to an excessive level which induces electrical and mechanical abnormalities in cardiac tissues. The electrical manifestations of Ca(2+) overload include arrhythmias caused by oscillatory (V(os)) and non-oscillatory (V(ex)) potentials. The mechanical manifestations include a decrease in force of contraction, contracture and aftercontractions. The underlying mechanisms involve a role of Na(+) in electrical abnormalities as a charge carrier in the Na(+)-Ca(2+) exchange and a role of Ca(2+) in mechanical toxicity. Ca(2+) overload may be induced by an increase in [Na(+)](i) through the inhibition of the Na(+)-K(+) pump (e.g. toxic concentrations of digitalis) or by an increase in Ca(2+) load (e.g. catecholamines). The Ca(2+) overload is enhanced by fast rates. Purkinje fibers are more susceptible to Ca(2+) overload than myocardial fibers, possibly because of their greater Na(+) load. If the SR is predominantly Ca(2+) overloaded, V(os) and fast discharge are induced through an oscillatory release of Ca(2+) in diastole from the SR; if the cytoplasm is Ca(2+) overloaded, the non-oscillatory V(ex) tail is induced at negative potentials. The decrease in contractile force by Ca(2+) overload appears to be associated with a decrease in high energy phosphates, since it is enhanced by metabolic inhibitors and reduced by metabolic substrates. The ionic currents I(os) and I(ex) underlie V(os) and V(ex), respectively, both being due to an electrogenic extrusion of Ca(2+) through the Na(+)-Ca(2+) exchange. I(os) is an oscillatory current due to an oscillatory release of Ca(2+) in early diastole from the Ca(2+)-overloaded SR, and I(ex) is a non-oscillatory current due to the extrusion of Ca(2+) from the Ca(2+)-overloaded cytoplasm. I(os) and I(ex) can be present singly or simultaneously. An increase in [Ca(2+)](i) appears to be involved in the short- and long-term compensatory mechanisms that tend to maintain cardiac output in physiological and pathological conditions. Eventually, [Ca(2+)](i) may increase to overload levels and contribute to cardiac failure. Experimental evidence suggests that clinical concentrations of digitalis increase force in Ca(2+)-overloaded cardiac cells by decreasing the inhibition of the Na(+)-K(+) pump by Ca(2+), thereby leading to a reduction in Ca(2+) overload and to an increase in force of contraction.

Animals↗