The purpose of this study was to determine whether the alternans of action potential duration (APD) occurring in Purkinje and ventricular muscle fibers after an abrupt shortening of cycle length can be explained by the two factors controlling the cycle length-dependent APD changes (i.e., restitution and memory effect). Action potentials were recorded simultaneously from dog Purkinje fibers and ventricular muscle fibers using conventional microelectrode techniques. APD change during alternans was dependent on the preceding diastolic interval in the same manner as during restitution in Purkinje fibers but not in ventricular muscle fibers. The course of memory change was not affected by the presence of alternans in either fiber type. In Purkinje fibers, APD alternans was attenuated by a Ca2+ channel blocker, nisoldipine (2 X 10(-6) M), and augmented by a Ca2+ channel agonist, Bay K 8644 (3 X 10(-8) M). These effects were attributed to the changes in the kinetics and the amplitude of restitution. In ventricular muscle fibers, APD alternans was always preceded and accompanied by alternans of action potential shape. Alternans of both action potential shape and APD was suppressed by nisoldipine (2 X 10(-6) M) and attenuated by Bay K 8644 (3 X 10(-8) M). These results show that in Purkinje fibers, APD during alternans can be explained by restitution and memory effect. However, in ventricular muscle fibers, the mechanism of APD alternans is linked to factors controlling action potential shape. These findings are compatible with the hypothesis that APD alternans in Purkinje fibers depends on the differences in the recovery of membrane currents generated by the preceding action potential and in ventricular muscle fibers on the differences in the concentration and/or handling of intracellular calcium.

An abrupt shortening of cycle length causes action potential duration (APD) alternation in both canine Purkinje (P) and ventricular (V) muscle fibers. Our recent study suggested that APD alternans is determined by the process controlling APD during electrical restitution in P but not in V fibers. In the latter, alternans was attributed to changes in the availability of intracellular calcium [Ca2"]j. We examined this hypothesis further with the following pharmacologic probes known to alter restitution or action of [Ca2"]1: tetradotoxin (0.5-3.0 ,lM), lidocaine HCI (2.0-12.0 jg/ml), sotalol (10 ,uM), nicorandil (10-20 ,M), 4-amino-pyridine (0.5 ,M), ryanodine (10 ,M), caffeine (2 mM), and ARL 115 BS (100 ,uM). Alternans in P fibers persisted under all studied conditions but varied in magnitude depending on the time constant and amplitude of restitution. In V fibers, the magnitude of alternans did not correlate with APD changes during restitution, and APD alternans was associated with the alternans of action potential shape and alternans of developed tension. Alternans in V was suppressed by caffeine at 2.0 mM [Ca2+], when tension was increased and by ryanodine at 1.0 mM [Ca2+]0 when tension was decreased. Alternans in V was not altered by changes in [Ca2+]. within the range of 1.0-4.0 mM; by ARL 115 BS, a compound that increases myofibrillar sensitivity to calcium; or by any other pharmacologic probes. We concluded that in P fibers, APD alternans was determined by the factors controlling APD in the absence of alternans; V fibers possess an independent mechanism of alternans linked to alternans of tension and controlled by [Ca2']

The purpose of these experiments was to determine whether or not acetylcholine modulated the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers. Conventional microelectrode techniques were used. Predictably, isoproterenol produced shortening of action potential duration; acetylcholine significantly blunted this effect of isoproterenol. Isoproterenol restored excitability to fibers exposed to 22 mM potassium solutions, and acetylcholine abolished this isoproterenol-restored excitability. Both of these antagonistic effects of acetylcholine were blocked by atropine. Acetylcholine alone did not affect action potential duration in polarized fibers or excitability in potassium-depolarized fibers. Furthermore, acetylcholine had no effect on the decrease in action potential duration induced by premature electrical stimulation or by acetylstrophanthidin administration, or on excitability of fibers exposed to a zero sodium, high calcium superfusant. These data demonstrate a direct cellular basis for cholinergic antagonism of the electrophysiological effects of beta-adrenergic stimulation of canine cardiac specialized intraventricular conducting tissue.

No abstract

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...