Dependence of delayed afterdepolarizations on diastolic potentials in ischemic Purkinje fibers

1989 ◽  
Vol 257 (3) ◽  
pp. H770-H777 ◽  
Author(s):  
W. B. Gough ◽  
N. el-Sherif
Keyword(s):  
Myocardial Infarction ◽  
Action Potentials ◽  
Resting Potential ◽  
Triggered Activity ◽  
Activity Maximum ◽  
Purkinje Fibers ◽  
Sustained Activity ◽  
Delayed Afterdepolarizations ◽  
Diastolic Potential

The mechanism of focal rhythms 1 day after myocardial infarction has been ascribed to both abnormal automaticity and triggered activity arising from delayed after-depolarizations (DADs). During the course of superfusion in vitro, diastolic potentials repolarize to more negative resting potentials. The dependence of DADs and triggered activity on diastolic potentials was studied using extrinsic currents. During sustained activity (maximum diastolic potential = -61 +/- 7 mV), hyperpolarizing current decreased the DADs, rendered them subthreshold, and terminated triggered activity. During the quiescence caused by constant hyperpolarizing current, a stimulated train of action potentials produced DADs. Decreasing the current permitted augmented DADs. In quiescent preparations (resting potential = -68 +/- 7 mV), a train of stimulated action potentials was followed by subthreshold DADs. Depolarizing current increased the DAD amplitude. To exclude depolarization-induced automaticity, constant currents were applied without a previous train of stimuli. Neither DADs nor triggered activity were evoked. Therefore, DADs and triggered activity, postinfarction, depend on the diastolic potential. There is a continuity between subthreshold DADs and sustained activity. DADs may reach a magnitude in which extrinsic interventions may not adequately terminate sustained triggered activity.

Acetylcholine lengthens action potentials of sheep cardiac Purkinje fibers

1980 ◽  
Vol 238 (2) ◽  
pp. H237-H243
Author(s):  
S. L. Lipsius ◽  
W. R. Gibbons
Keyword(s):  
Muscarinic Receptors ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Purkinje Fibers ◽  
Diastolic Depolarization ◽  
Cardiac Purkinje Fibers ◽  
Rate Of Increase ◽  
Definite Sequence ◽  
Microelectrode Techniques ◽  
Diastolic Potential

The effect of acetylcholine (ACh) on the electrical activity of sheep cardiac Purkinje fibers was studied using standard microelectrode techniques. Most fibers showed a definite sequence of changes when exposed to ACh. Initially, action potential duration (APD) increased markedly. After about 20 s, the maximum diastolic potential (MDP) started to become more negative and, at the same time, the rate of increase in APD slowed. Once the MDP stabilized at a more negative level, the APD usually resumed its rapid increase. ACh also increased the slope of diastolic depolarization and made the plateau voltage more positive. APD was increased by ACh concentrations as low as 10(-7) M, and it increased with concentrations up to 10(-5) M (the highest concentration tested). ACh-induced increases in APD depended on the stimulation frequency; 2-min exposures to 10(-6) M ACh increased APD by 76.8 +/- 14.7% at 6 min-1 and 17.7 +/- 4.2% at 60 min-1. Atropine blocked all the effects of ACh. Hexamethonium did not prevent the ACh effects. It is concluded that ACh acts via muscarinic receptors. The changes in APD and MDP appear to be separate events, and it is difficult to see how the former effect may be explained by known actions of ACh.

Abstract 1236: A Molecular and Functional Basis for Focal Arrhythmogenesis in Heart Failure-associated Atrial Fibrillation

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yung-Hsin Yeh ◽  
Reza Wakili ◽  
Xiao Yan Qi ◽  
Denis Chartier ◽  
Stefan Kääb ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Protein Expression ◽  
Action Potentials ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Regulatory Proteins ◽  
Related Protein ◽  
Triggered Activity ◽  
Delayed Afterdepolarizations

Introduction: Heart failure (HF) frequently causes atrial fibrillation (AF) and focal sources of unknown mechanism have been implicated. Here, we studied the potential role and molecular mechanisms of Ca 2+ handling abnormalities. Methods: Ca 2+ handling (microfluorescence, Indo-1 AM) and related protein expression (Western blot) were assessed in left atria of 20 dogs with ventricular tachypacing (240 bpm × 2 wks)-induced HF and 20 controls (CTLs). Whole-cell perforated-patch was used to record action potentials (APs), delayed afterdepolarizations (DADs) and triggered activity. Results : HF increased [Ca 2+ ] i transient amplitude from 239±24 to 444±43* nM (*P<0.05), and [Ca 2+ ] i release by 10 mM local caffeine puffs (an index of SR Ca 2+ content) from 849±71 (CTL) to 1574±169* nM (HF). Spontaneous Ca 2+ release events increased from 1.8±0.5 (CTL) to 10.7±2.1* events/run (HF). HF significantly increased APD (by ~40% at 1 Hz). DADs and triggered activity were more common in HF (15.2±2.6 triggered APs/run, vs CTL 0.4±0.2*), and were abolished by ryanodine (10 μM), but not by the I f -blocker Cs + (2 mM). HF caused profound changes in protein expression of key Ca 2+ handling and regulatory proteins (Table ). Calsequestrin, the major SR Ca 2+ -binding protein, was reduced by 32%*. Fractional RYR2 PKA (Ser2809) phosphorylation decreased by 63%*, whereas CaMKII (Ser2815) RYR2 phosphorylation increased by 221%*. The catalytic and regulatory (RII) PKA subunits were downregulated by 15%* and 73%*, whereas expression and autophosphorylation (Thr287) of CaMKIIδ were increased by 45%* and 81%* respectively. NCX1, SERCA and total, PKA and CaMKII phosphorylated SERCA-regulatory phospholamban were unchanged by HF. Conclusions: HF causes profound changes in regulation and expression of atrial Ca 2+ handling proteins, producing increased SR Ca 2+ load and release, along with DADs and triggered activity that may account for focal mechanisms that initiate and/or sustain HF-related AF.

Characterization of an early afterhyperpolarization after a brief train of action potentials in rat hippocampal neurons in vitro

1990 ◽  
Vol 63 (1) ◽  
pp. 72-81 ◽  
Author(s):  
A. Williamson ◽  
B. E. Alger
Keyword(s):  
Action Potentials ◽  
Hippocampal Neurons ◽  
Pyramidal Cells ◽  
Chloride Ions ◽  
Membrane Potentials ◽  
Resting Potential ◽  
K Channel ◽  
Delayed Rectifier ◽  
Extracellular Potassium

1. In rat hippocampal pyramidal cells in vitro, a brief train of action potentials elicited by direct depolarizing current pulses injected through an intracellular recording electrode is followed by a medium-duration afterhyperpolarization (mAHP) and a longer, slow AHP. We studied the mAHP with the use of current-clamp techniques in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (cAMP) to block the slow AHP and isolate the mAHP. 2. The mAHP evoked at hyperpolarized membrane potentials was complicated by a potential generated by the anomalous rectifier current, IQ. The mAHP is insensitive to chloride ions (Cl-), whereas it is sensitive to the extracellular potassium concentration ([K+]o). 3. At slightly depolarized levels, the mAHP is partially Ca2+ dependent, being enhanced by increased [Ca2+]o and BAY K 8644 and depressed by decreased [Ca2+]o, nifedipine, and Cd2+. The Ca2(+)-dependent component of the mAHP was also reduced by 100 microM tetraethylammonium (TEA) and charybdotoxin (CTX), suggesting it is mediated by the voltage- and Ca2(+)-dependent K+ current, IC. 4. Most of the Ca2(+)-independent mAHP was blocked by carbachol, implying that IM plays a major role. In a few cells, a small Ca2(+)- and carbachol-insensitive mAHP component was detectable, and this component was blocked by 10 mM TEA, suggesting it was mediated by the delayed rectifier current, IK. The K+ channel antagonist 4-aminopyridine (4-AP, 500 microM) did not reduce the mAHP. 5. We infer that the mAHP is a complex potential due either to IQ or to the combined effects of IM and IC. The contributions of each current depend on the recording conditions, with IC playing a role when the cells are activated from depolarized potentials and IM dominating at the usual resting potential. IQ is principally responsible for the mAHP recorded at hyperpolarized membrane potentials.

Toxic effects of ouabain on Purkinje fibers and ventricular muscle fibers

1962 ◽  
Vol 203 (3) ◽  
pp. 433-439 ◽  
Author(s):  
Mario Vassalle ◽  
Johannes Karis ◽  
Brian F. Hoffman
Keyword(s):  
Muscle Fibers ◽  
Toxic Effects ◽  
Resting Potential ◽  
Ventricular Muscle ◽  
Purkinje Fibers ◽  
Diastolic Depolarization ◽  
Series Of Experiments ◽  
Time Required ◽  
Induced Changes

Toxic effects of ouabain on single Purkinje fibers and ventricular muscle fibers were investigated in vitro by microelectrode technique. Toxicity developed much earlier in the specialized conducting fibers and consisted of a progressively increasing rate of diastolic depolarization and a decrease of amplitude and duration of the action potential. The majority of Purkinje fiber preparations developed extrasystoles and rapid spontaneous rhythms. The resting potential was much decreased. The ouabain-induced changes in ventricular muscle fibers occurred much later than did changes in Purkinje fibers and consisted of a decrease in the plateau and in the amplitude of the action and resting potential. Spontaneous depolarization was not observed in muscle fibers. The effect of the rate of stimulation on the development of ouabain toxicity was studied in another series of experiments on driven and quiescent muscles. Signs of toxicity appeared earlier in the driven muscles than in duplicate quiescent muscles and, at faster rates of stimulation, the time required for the toxic changes was shortened.

Abnormal Action Potential Responses to Halothane in Heart Muscle Isolated from Malignant Hyperthermia-susceptible Pigs

1995 ◽  
Vol 82 (4) ◽  
pp. 947-953. ◽  
Author(s):  
Norbert Roewer ◽  
Clemens Greim ◽  
Eckhart Rumberger ◽  
Jochen Schulte am Esch
Keyword(s):  
Malignant Hyperthermia ◽  
Action Potentials ◽  
Myocardial Function ◽  
In Vitro Study ◽  
Resting Potential ◽  
Cardiac Symptoms ◽  
Cardiac Dysrhythmias ◽  
Malignant Hyperthermia Susceptible ◽  
The Right

Background During human and porcine malignant hyperthermia (MH), cardiac dysrhythmias and altered myocardial function can be observed. It is unknown whether a primary abnormality in cardiac muscle contributes to the cardiac symptoms during MH. An abnormal response to halothane has recently been demonstrated in action potentials (APs) from MH-susceptible (MHS) human skeletal muscles. We investigated the electrophysiologic properties in trabeculae isolated from the right ventricles of normal (MHN) and MHS pigs. Methods The experiments were performed on electrically stimulated (1 Hz) trabeculae isolated from the right ventricles of MHS and MHN pigs. Resting membrane potentials, APs, and tension were measured with and without the presence of 1% halothane. In addition, the halothane-equilibrated muscles were exposed to caffeine in increasing doses (1, 2, and 4 mM). Results In the absence of halothane, resting potential and AP characteristics in MHS and MHN muscles did not differ significantly. Halothane did not alter resting potentials but produced different alterations in the APs in MHS and MHN muscles, whereas the decrease in twitch tension was identical. In contrast to reductions in the AP amplitude and duration in MHN muscle, halothane produced an enlargement of the APs in MHS muscle. The addition of caffeine caused nearly identical prolongations of AP duration in MHS and MHN muscles. Conclusions This in vitro study demonstrates that halothane produces abnormal alterations in the dynamic electric properties of the ventricular excitable membrane from MHS pigs. These results suggest a latent defect in the myocardium of MHS pigs that becomes apparent in the presence of MH-triggering agents.

Excitability and oscillatory afterpotentials in isolated sheep cardiac Purkinje fibers

1987 ◽  
Vol 252 (3) ◽  
pp. H645-H652 ◽  
Author(s):  
R. M. Terek ◽  
C. T. January
Keyword(s):  
Action Potentials ◽  
Control Level ◽  
Time Dependent ◽  
Resting Potential ◽  
Purkinje Fibers ◽  
Conduction Disturbances ◽  
Cardiac Purkinje Fibers ◽  
Cycle Lengths ◽  
Current Threshold ◽  
The Mean

Oscillatory afterpotentials, or late afterdepolarizations, are one mechanism postulated to cause cardiac arrhythmias and possibly conduction disturbances. We studied excitability by determining strength-interval curves in Purkinje fibers under normal conditions and during the presence of oscillatory afterpotentials induced by cardiac glycoside toxicity. During exposure to acetylstrophanthidin (0.10–0.15 mg/l), the mean resting potential depolarized 5.6 mV and oscillatory afterpotentials of 3–17 mV appeared. Current threshold for evoking action potentials was reduced below control level (e.g., increased excitability) throughout electrical diastole. Associated with oscillatory afterpotentials was a marked biphasic variation in current threshold giving strength-interval curves a characteristic biphasic shape. During the rising phase of the oscillatory afterpotentials, excitability reached a maximum, whereas the minimum increase in excitability occurred during the falling phase of oscillatory afterpotentials. This biphasic change in excitability remained correlated with the oscillatory afterpotentials at different cycle lengths. Results show that during acetylstrophanthidin toxicity excitability is increased throughout electrical diastole, and characteristic time-dependent changes in excitability occur during oscillatory afterpotentials. Time-dependent changes in excitability were detected with both intra- and extracellular stimulation techniques.

scholarly journals Induction of delayed afterdepolarizations and triggered activity in canine Purkinje fibers by lysophosphoglycerides.

1986 ◽  
Vol 59 (4) ◽  
pp. 416-426 ◽  
Author(s):  
S M Pogwizd ◽  
J R Onufer ◽  
J B Kramer ◽  
B E Sobel ◽  
P B Corr
Keyword(s):  
Triggered Activity ◽  
Purkinje Fibers ◽  
Delayed Afterdepolarizations

I NaCa andI Cl(Ca)contribute to isoproterenol-induced delayed afterdepolarizations in midmyocardial cells

1998 ◽  
Vol 275 (6) ◽  
pp. H1979-H1992 ◽  
Author(s):  
Andrew C. Zygmunt ◽  
Robert J. Goodrow ◽  
Charlene M. Weigel
Keyword(s):  
Reversal Potential ◽  
Outward Current ◽  
Resting Potential ◽  
Triggered Activity ◽  
Cation Conductance ◽  
Outward Currents ◽  
Calcium Loading ◽  
Inward Currents ◽  
Delayed Afterdepolarizations ◽  
Calcium Exchange

The contributions of electrogenic sodium/calcium exchange current ( I NaCa), calcium-activated chloride conductance [ I Cl(Ca)], and calcium-activated nonselective cation conductance to delayed afterdepolarizations (DAD) were examined. Nonselective cation channels were absent in canine M cells, since inhibition of I NaCa and I Cl(Ca)eliminated all calcium-activated currents without abolishing cell shortening. After the cells were treated with isoproterenol and ouabain to increase calcium loading, I NaCa was 168 ± 30 × 10−3 pC/pF and I Cl(Ca) was 114 ± 24 × 10−3pC/pF. Transient overlapping inward and outward currents were evoked positive to the chloride reversal potential ( E Cl). Outward current was chloride sensitive, and inward current was blocked by replacement of external sodium with lithium. When E Cl was −50 mV, triggered activity occurred in normal external sodium and persisted after inhibition of I NaCa. Steps to −80 mV revealed oscillating inward currents in normal sodium and chloride, which persisted after inhibition of I NaCa. When E Cl was equal to −113 mV, I Cl(Ca) opposed I NaCa at the resting potential. DAD occurred in normal sodium, and inhibition of outward I Cl(Ca)provoked triggered activity. We conclude that I NaCa represents ∼60% of the total calcium-activated current at resting potentials but that both I NaCa and I Cl(Ca) work in concert to cause DAD in calcium-overloaded cells.

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