Analysis of cardiac pacemaker potential using a "voltage clamp" technique

Vassalle, Mario

doi:10.1152/ajplegacy.1966.210.6.1335

Cited by 189 publications

(133 citation statements)

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“…McAllister & Noble 1966) that the initial excitatory sodium current is not completely inactivated since in most instances the slow current starts as inward current and may even stay in the inward direction at a certain potential. Furthermore, McAllister & Noble (1967) do not exclude the possibility that slow inactivation of gNa contributes to the early part of the slow current change, as Vassalle (1966) suggested from his results. This view would conflict with the results of Dudel et al (1966bDudel et al ( , 1967b which suggest a rapid and almost complete inactivation of the sodium current.…”

Section: Resultsmentioning

confidence: 81%

“…Thus, a slow and incomplete (McAllister & Noble, 1966) inactivation Of 9Na could not be confirmed by Dudel et al (1966b). They found a rapid and almost complete inactivation of 9Na and, in contrast to Vassalle (1966) and McAllister & Noble (1966, 1967, no component of delayed rectification of gE (Dudel et al 1967c). These points, however, are important for the explanation of the plateau of the cardiac action potential.…”

Section: Introductionmentioning

confidence: 95%

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Slow inactivation of currents in cardiac Purkinje fibres

Réuter¹

1968

The Journal of Physiology

104

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SUMMARY1. When membrane currents, associated with repolarization to the holding potential, were measured in cardiac Purkinje fibres after depolarizing voltage clamp steps to the plateau level of the action potential ( -20 to -10 mV), tails of inward current were observed which turned into outward current. Amplitude and duration of the tails of inward current increased when the preceding depolarization was progressively shortened. This current could only be recorded in Na-containing solution which strongly supports the view that the inactivation of sodium conductance (gNa) has a slow and incomplete component.2. Initial outward current (most probably chloride current (Ic,)) during strong depolarization (beyond -20 mV) could be inactivated either by increasing the frequency of depolarizations or by applying a conditioning depolarizing prepulse.3. In Na-free solution a small, slowly decreasing inward current was recorded. This is most probably carried by calcium ions and is at least partly responsible for the negative conductance of the current-voltage relation in the voltage range -60 to -30 mV.4 the action potential and (ii) calcium ions carry additional charge during this phase of the action potential. Chloride conductance (gcl) should be largely inactivated at a heart rate of 90/min.

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Section: Resultsmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 95%

Slow inactivation of currents in cardiac Purkinje fibres

Réuter¹

1968

The Journal of Physiology

104

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“…The characteristic phase 4 decline of the transmembrane potential of these cardiac cells may be the consequence of decreased potassium conductance during electrical diastole (5)(6)(7)(8). A slow influx of sodium concomitant with the reduced potassium conductance results in a net inward current of positively charged ions which gradually reduces the transmembrane potential to threshold.…”

Section: Discussionmentioning

confidence: 99%

Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

Bailey

Greenspan

Elizari

et al. 1972

Circulation Research

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Conventional intracellular recordings from the bundle of His and right bundle branch of the canine heart demonstrated that the slope of diastolic depolarization is markedly depressed by superfusion with relatively small concentrations (4-8 jug/ml) of acetylcholine. As the cells become less automatic, take-off potential increases, rise time of phase 0 is reduced, action potential amplitude increases, and conduction proceeds more rapidly.KEY WORDS right bundle branch determinants of conductivity spontaneous phase 4 depolarization transmembrane action potential innervation of the heart • Early investigations indicated that cells of the specialized conduction system below the atrioventricular (AV) junction are unaffected by small concentrations of acetylcholine (1). Specifically, the slope of spontaneous phase 4 depolarization from cells of the bundle of His, bundle branches, and peripheral Purkinje fibers is reported to be essentially unchanged by the infusion of acetylcholine. A method of exposing the entire proximal portion of the specialized AV conduction system of the canine heart in vitro was devised by one of the authors (M.V.E.), and the regular observation of automaticity afforded the opportunity to reexamine certain aspects of this property.From the Krannert Institute of Cardiology, Marion County General Hospital, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.This work was supported in part by U. S. Public Health Service Grants HE-6308, HTS-5363, and HE-5749 from the National Heart Institute and by the Herman C. Krannert Fund, the Indiana Heart Association, and the AMA Committee for Research on Tobacco and Health. Drs. Bailey, Elizari, and Anderson are U. S. Public Health Service Trainees in Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.Received July 30, 1971. Accepted for publication November 29, 1971. The purpose of this paper is to report our studies of the effects of small doses of acetylcholine on spontaneity and conduction within the proximal portion of the HisPurkinje conduction pathways. MethodsAdult mongrel dogs of either sex weighing 15-20 kg were anesthetized with sodium pentobarbital (30 mg/kg, i.v.) and intubated; respiration was controlled with a Harvard respirometer. The hearts were excised rapidly through a right thoracotomy, and the portion of the septum containing the AV junction, the bundle of His, and both bundle branches was removed, placed in a Lucite muscle chamber, and superfused with oxygenated Tyrode's solution maintained at a temperature of 31 ± 0.2°C. Then the entire bundle of His was exposed from the nodal His (NH) region of the AV junction to the origins of both bundle branches. Portions of the proximal part of the specialized AV conduction system were isolated, when appropriate, by transection. The tissue was then allowed to stabilize for several hours until muscular contraction ceased and to minimize changes in diastolic depolarization as a function of time and in...

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“…The rabbit preparation seems promising for future analysis of outward plateau currents. Unlike sheep or calf Purkinje fibres, the rabbit preparations do not show slow current changes characteristic of the pacemaker K current, IK, (Vassalle, 1966;Noble & Tsien, 1968). The absence of pacemaker current changes is not readily explained by the dissection or voltage clamp procedures since earlier recordings show a corresponding lack of IK2-dependent pacemaker activity in peripheral Purkinje tissue in situ (p. 230).…”

Section: Time-dependent Outward Currentsmentioning

confidence: 99%

“…7-16). The virtual absence of pace-maker activity in fully polarized rabbit Purkinje fibres is the main electrical characteristic distinguishing them from sheep or calf Purkinje fibres, which regularly exhibit phase 4 depolarization (Draper RABBIT PURKINJE FIBRE MEMBRANE CURRENTS & Weidmann, 1951;Vassalle, 1966). In respect, the rabbit preparation may be similar to Purkinje fibres from several other species which have little or no diastolic depolarization under normal conditions (Hoffman & Cranefield, 1960, p. 176).…”

Section: Resting and Action Potentialsmentioning

confidence: 99%

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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Analysis of cardiac pacemaker potential using a "voltage clamp" technique

Cited by 189 publications

References 0 publications

Slow inactivation of currents in cardiac Purkinje fibres

Slow inactivation of currents in cardiac Purkinje fibres

Effects of Acetylcholine on Automaticity and Conduction in the Proximal Portion of the His-Purkinje Specialized Conduction System of the Dog

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

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