Investigations of the Electrical Properties of Cardiac Muscle Fibres with the Aid of Intracellular Double-Barrelled Electrodes

Johnson, Edward A.; Tille, J.

doi:10.1085/jgp.44.3.443

Cited by 33 publications

(14 citation statements)

References 8 publications

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“…In the double sucrose gap, the rabbit preparations were partially depolarized and only gave regenerative responses after a hyperpolarizing current pulse. The responses were triangular and lacked the fully developed plateau seen with micro-electrode recordings from Purkinje fibres in situ (Hoffman & Cranefield, 1960;Johnson & Tille, 1961;Gibbs & Johnson, 1961) or isolated preparations (this paper). The I-V relations in the sucrose gap (Harrington 245 T. J.…”

mentioning

confidence: 72%

Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres.

Colatsky¹,

Tsien²

1979

The Journal of Physiology

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SUMMARY1. Rabbit Purkinje fibres were studied using micro-electrode recordings of electrical activity or a two-micro-electrode voltage clamp. Previous morphological work had suggested that these preparations offer structural advantages for the analysis of ionic permeability mechanisms.2. Viable preparations could be obtained consistently by exposure to a K glutamate Tyrode solution during excision and recovery. In NaCl Tyrode solution, the action potential showed a large overshoot and fully developed plateau, but no pacemaker depolarization at negative potentials.3. The passive electrical properties were consistent with morphological evidence for the accessibility of cleft membranes within the cell bundle. Electrotonic responses to intracellular current steps showed the behaviour expected for a simple leaky capacitative cable. Capacitative current transients under voltage clamp were changed very little by an eightfold reduction in the external solution conductivity.4. Slow current changes attributable to K depletion were small compared to those found in other cardiac preparations. The amount of depletion was close to that predicted by a cleft model which assumed free K diffusion in 1 ,sm clefts. 5. Step depolarizations over the plateau range of potentials evoked a slow inward current which was resistant to tetrodotoxin but blocked by D600. 6. Strong depolarizations to potentials near 0 mV elicited a transient outward current and a slowly activating late outward current. Both components resembled currents found in sheep or calf Purkinje fibres.7. These experiments support previous interpretations of slow plateau currents in terms of genuine permeability changes. The rabbit Purkinje fibre may allow various ionic channels to be studied with relatively little interference from radial non-uniformities in membrane potential or ion concentration.

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confidence: 72%

Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres.

Colatsky¹,

Tsien²

1979

The Journal of Physiology

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“…Input resistance was measured with double-barrelled microelectrodes (Johnson and Tille, 1961). A current pulse, 5x 10~8 A and 100 msec, was injected through one barrel and the other was used for recording the potential drop (Fig.…”

Section: Methodsmentioning

confidence: 99%

Decreased intercellular coupling after prolonged rapid stimulation in rabbit atrial muscle.

Brėdikis

Bukauskas²,

Veteikis

1981

Circulation Research

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SUMMARY Driving rabbit atrial trabeculae at a rapid rate for 15 minutes resulted in a decrease in the space constant for electrotonic decay from an average of 670 to 400 ;im. Input resistance, Ru,, as measured by use of a double-barrelled microelectrode, increased from a mean value of 380 kOhms to one of 600 kOhms. The time to return to control values after the end of rapid driving was 20-60 minutes. Similar effects of rapid driving were observed in the presence of atropine, propranolol, and atropine plus propranolol and phentolamine. According to the theory of current spread in a three-dimensional syncytium, a rise of input resistance should be interpreted mainly as an increase of cell-to-cell resistance. We advance the hypothesis that, when driven at their maximal possible rate (or when fibrillating), cardiac cells gain Na + and Ca 1 *, and that this results in partial but reversible uncoupling.

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“…Both simulations using our model and previous experimental recordings (7,9) show an almost flat resting phase (rate of depolarization 0.2 mV/ms) in rabbit Purkinje cells. The lack of pacemaker activity in rabbit Purkinje cells, unlike in other species like the sheep, has been consistently shown under physiological conditions in situ in the intact cardiac wall (19), in isolated strands of Purkinje fibers (7), and also in isolated myocytes (9,10,16). Simulations were also conducted to determine the dependence of the simulated AP on stimulation rate.…”

Section: Rabbit Purkinje Ap and Its Dependence With Extracellular Kmentioning

confidence: 99%

Ionic mechanisms of electrophysiological properties and repolarization abnormalities in rabbit Purkinje fibers

Corrias

Giles

Rodríguez

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Corrias A, Giles W, Rodriguez B. Ionic mechanisms of electrophysiological properties and repolarization abnormalities in rabbit Purkinje fibers. Am J Physiol Heart Circ Physiol 300: H1806-H1813, 2011. First published February 18, 2011 doi:10.1152/ajpheart.01170.2010.-Purkinje cells play an important role in drug-induced arrhythmogenesis and are widely used in preclinical drug safety assessments. Repolarization abnormalities such as action potential (AP) prolongation and early afterdeploarizations (EAD) are often observed in vitro upon pharmacological interventions. However, because drugs do not act on only one defined target, it is often difficult to fully explain the mechanisms of action and their potential arrhythmogenicity. Computational models, when appropriately detailed and validated, can be used to gain mechanistic insights into the mechanisms of action of certain drugs. Nevertheless, no model of Purkinje electrophysiology that is able to reproduce characteristic Purkinje responses to drug-induced changes in ionic current conductances such as AP prolongation and EAD generation currently exists. In this study, a novel biophysically detailed model of rabbit Purkinje electrophysiology was developed by integration of data from voltage-clamp and AP experimental recordings. Upon validation, we demonstrate that the model reproduces many key electrophysiological properties of rabbit Purkinje cells. These include: AP morphology and duration, both input resistance and rate dependence properties as well as response to hyperkalemia. Pharmacological interventions such as inward rectifier K ϩ current and rapid delayed rectifier K ϩ current block as well as late Na ϩ current increase result in significant AP changes. However, enhanced L-type Ca 2ϩ current (iCaL) dominates in EAD genesis in Purkinje fibers. In addition, iCaL inactivation dynamics and intercellular coupling in tissue strongly modulate EAD formation. We conclude that EAD generation in Purkinje cells is mediated by an increase in iCaL and modulated by its inactivation kinetics. electrophysiology; Purkinje; early afterdepolarization; arrhythmia FOR DECADES, PURKINJE FIBERS have been implicated in the initiation of lethal cardiac arrhythmias such as ventricular fibrillation and Torsades de Pointes in a variety of clinical situations. In patients with congenital long QT syndrome or Brugada syndrome, for example, the Purkinje-myocardial interface is often the location where ventricular fibrillation initiated (15). Adverse side effects of drugs belonging to a broad range of categories are important factors that have long been associated with arrhythmogenesis. Regulatory agencies have identified Purkinje fibers as an important tool in preclinical assessment of drug safety. Both the Food and Drug Administration and the European Medicines Agency recommend the Purkinje fiber assay for in vitro electrophysiological studies as valuable for assessing potential arrhythmogenicity of a tested compound (41). Aubert et al. (2) have specifically evaluated the rabbit Purkinj...

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Investigations of the Electrical Properties of Cardiac Muscle Fibres with the Aid of Intracellular Double-Barrelled Electrodes

Cited by 33 publications

References 8 publications

Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres.

Electrical properties associated with wide intercellular clefts in rabbit Purkinje fibres.

Decreased intercellular coupling after prolonged rapid stimulation in rabbit atrial muscle.

Ionic mechanisms of electrophysiological properties and repolarization abnormalities in rabbit Purkinje fibers

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