Role of voltage oscillations in the automaticity of sheep cardiac Purkinje fibers

1995 ◽  
Vol 73 (8) ◽  
pp. 1165-1180 ◽  
Author(s):  
Peter A. Spiegler ◽  
Mario Vassalle
Keyword(s):  
Action Potential ◽  
Spontaneous Activity ◽  
Oscillatory Potentials ◽  
Extracellular Calcium ◽  
Calcium Overload ◽  
Spontaneous Discharge ◽  
Extracellular Potassium ◽  
Purkinje Fibers ◽  
Diastolic Depolarization

The role of oscillatory potentials occurring near the threshold for the fast sodium current (ThVos) in the induction of spontaneous and repetitive activity was studied in sheep Purkinje fibers superfused in vitro. In low extracellular potassium concentration, the steepness and amplitude of diastolic depolarization increased and ThVos appeared during quiescence. ThVos amplitude increased progressively until its depolarizing phase reached the threshold potential for the initiation of the action potential. Drive increased the amplitude of diastolic depolarization and of ThVos, and longer drives induced faster and longer-lasting repetitive activity ("overdrive excitation"). In quiescent fibers, barium depolarized the resting membrane and initiated spontaneous discharge through ThVos. Acetylcholine had similar actions. Cesium hyperpolarized the membrane, thereby suppressing ThVos and related spontaneous activity. Tetrodotoxin and lidocaine also suppressed ThVos, but not the driven action potentials. In low extracellular potassium plus high extracellular calcium concentrations, drive induced ThVos as well as the oscillatory potentials related to calcium overload (Vos), but caused overdrive excitation through ThVos, even when caffeine was present. We conclude from our results that in Purkinje "dominant" pacemaker fibers (i) diastolic depolarization initiates spontaneous activity by attaining the threshold for the upstroke of the action potential through the depolarizing phase of a ThVos; (ii) the depolarizing phase of ThVos is caused by a tetrodotoxin-sensitive Na+ component; (iii) ThVos is voltage dependent in that a small depolarization of the resting membrane induces it and a small hyperpolarization suppresses it; (iv) ThVos can induce overdrive excitation; and (v) ThVos occurs in the absence of calcium overload and has distinguishing characteristics from the Vos induced by calcium overload.Key words: automaticity, overdrive excitation, barium, acetylcholine, cesium, tetrodotoxin, lidocaine, high extracellular calcium, low extracellular potassium.

Different forms of spontaneous discharge induced by strophanthidin in cardiac Purkinje fibers

1982 ◽  
Vol 243 (5) ◽  
pp. H767-H778
Author(s):  
S. Ishikawa ◽  
M. Vassalle
Keyword(s):  
Oscillatory Potentials ◽  
Spontaneous Discharge ◽  
Purkinje Fibers ◽  
Diastolic Depolarization ◽  
Cardiac Purkinje Fibers ◽  
High Calcium ◽  
Low Potassium ◽  
Slow Rhythm ◽  
Fast Rhythm

The effect of strophanthidin on spontaneous discharge in canine cardiac Purkinje fibers perfused in vitro was studied during periodic interruptions (pauses) of the electrical drive. The results show that 1) strophanthidin initially increases the slope of diastolic depolarization and thereby induces a slow rhythm that accelerates progressively during the pause and becomes faster during the increasing strophanthidin inotropy; 2) oscillatory potentials appear only when strophanthidin inotropy reaches its peak (or actually declines) and may cause either a few fast action potentials during the pause or a fast rhythm that eventually overcomes the driven beats; 3) the slow rhythm is eliminated by cesium; 4) the fast rhythm is eliminated by tetrodotoxin; and 5) oscillatory potentials caused by high calcium, norepinephrine, or low potassium are similarly affected by cesium or tetrodotoxin. It is concluded that strophanthidin enhances diastolic depolarization, thereby causing the slow rhythm, and induces oscillatory potentials, thereby causing the fast rhythm. Only the oscillatory potentials are related to calcium overload as determined by several different procedures.

Effect of tetraethylammonium chloride on action potential in cardiac Purkinje fibers

1981 ◽  
Vol 241 (2) ◽  
pp. H139-H144
Author(s):  
S. Ito ◽  
B. Surawicz
Keyword(s):  
Action Potential ◽  
Outward Current ◽  
Extracellular Potassium ◽  
Tetraethylammonium Chloride ◽  
Purkinje Fibers ◽  
Extracellular Potassium Concentration ◽  
Cardiac Purkinje Fibers ◽  
Prolonged Action Potential Duration ◽  
Diastolic Potential

Intracellular loading with 20 mM tetraethylammonium chloride (TEA) diffusing through the cut end of the preparations prolonged action potential duration (APD) in dog Purkinje fibers without changing maximum diastolic potential, overshoot, and dV/dtmax. The APD was prolonged at all rates of stimulation, but, contrary to the normal rules, APD increased more after longer than after shorter interstimulus intervals. TEA increased the number of beats required to achieve the new steady-state APD after an abrupt change in the rate of stimulation. The effect of varying extracellular potassium concentration on maximal diastolic potential suggested that intracellular loading with TEA had no effect on the time-independent "background" outward current (IK1). If we ascribe all observed TEA effects to the reduction of time dependent slow outward current Ix1, we can propose a hypothesis concerning the role of Ix1 in the regulation of APD at slow heart rates.

Action potential propagation through embryonic dorsal root ganglion cells in culture. II. Decrease of conduction reliability during repetitive stimulation

1994 ◽  
Vol 72 (2) ◽  
pp. 634-643 ◽  
Author(s):  
C. Luscher ◽  
J. Streit ◽  
P. Lipp ◽  
H. R. Luscher
Keyword(s):  
Dorsal Root Ganglion ◽  
Action Potential ◽  
Intracellular Calcium ◽  
Dorsal Root ◽  
Channel Blocker ◽  
Extracellular Calcium ◽  
Repetitive Stimulation ◽  
Calcium Currents ◽  
Double Pulse ◽  
Extracellular Potassium

1. The reliability of the propagation of action potentials (AP) through dorsal root ganglion (DRG) cells in embryonic slice cultures was investigated during repetitive stimulation at 1–20 Hz. Membrane potentials of DRG cells were recorded intracellularly while the axons were stimulated by an extracellular electrode. 2. In analogy to the double-pulse experiments reported previously, either one or two types of propagation failures were recorded during repetitive stimulation, depending on the cell morphology. In contrast to the double-pulse experiments, the failures appeared at longer interpulse intervals and usually only after several tens of stimuli with reliable propagation. 3. In the period with reliable propagation before the failures, a decrease in the conduction velocity and in the amplitude of the afterhyperpolarization (AHP), an increase in the total membrane conductance, and the disappearance of the action potential “shoulder” were observed. 4. The reliability of conduction during repetitive stimulation was improved by lowering the extracellular calcium concentration or by replacing the extracellular calcium by strontium. The reliability of conduction decreased by the application of cadmium, a calcium channel blocker, 4-amino pyridine, a fast potassium channel blocker, or apamin or muscarine, the blockers of calcium-dependent potassium channels. The reliability of conduction was not effected by blocking the sodium potassium pump with ouabain or by replacing extracellular sodium with lithium. 5. In the period with reliable propagation cadmium, apamin, and muscarine reduced the amplitude of the AHP. The shoulder of the action potential was more pronounced and not sensitive to repetitive stimulation when extracellular calcium was replaced by strontium. It disappeared when cadmium was applied. 6. In DRG somata changes of the intracellular Ca2+ concentration were monitored by measuring the fluorescence of the Ca2+ indicator Fluo-3 with a laser-scanning confocal microscope. During repetitive stimulation, an accumulation of intracellular calcium occurred that recovered very slowly (tens of seconds) after the AP trains. 7. Computer model simulations performed in analogy to the experimental protocols produced conduction failures during repetitive stimulation only when the calcium currents during the APs were reduced. 8. From these findings it is concluded that conduction failures during repetitive stimulation are dependent on an accumulation of intracellular calcium leading to an inactivation of calcium currents, combined with small contributions of an accumulation of extracellular potassium and a summation of slow potassium conductances.

Role of acetylcholine in induction of repetitive activity in human atrial fibers

1989 ◽  
Vol 256 (1) ◽  
pp. H74-H84
Author(s):  
Z. Y. Hou ◽  
C. I. Lin ◽  
M. Vassalle ◽  
B. N. Chiang ◽  
K. K. Cheng
Keyword(s):  
Action Potential ◽  
Muscarinic Receptor ◽  
Action Potentials ◽  
Oscillatory Potentials ◽  
Contractile Force ◽  
Intracellular Level ◽  
Transmembrane Potentials ◽  
Rebound Increase

The actions of acetylcholine and its interactions with epinephrine were studied in human atrial tissues by recording transmembrane potentials and contractile force. Acetylcholine (0.55-5.5 microM) reduced force, shortened the duration and shifted to more negative values the plateau of action potentials, abolished phase 4 depolarization, and suppressed the activity of spontaneous fibers. During the recovery, often there was a rebound increase in some parameters of the action potential and in force. Epinephrine (0.3-2.8 microM) induced oscillatory potentials and aftercontractions and acetylcholine abolished them. However, during the washout of acetylcholine in the presence of epinephrine, the oscillatory potentials and aftercontractions were larger than before acetylcholine, and repetitive activity was often induced. The inhibitory and excitatory effects of acetylcholine were mimicked by methacholine (5.1 microM) and abolished by atropine (1.5 microM). The postacetylcholine rebound was also potentiated by theophylline (0.6-2 mM) but was not blocked by propranolol (1-3.4 microM), prazosin (1 microM), and diltiazem (0.1 microM). It is concluded that in human atrial fibers acetylcholine has inhibitory as well as excitatory effects that are exaggerated in the presence of epinephrine and are mediated by the activation of the muscarinic receptor. The interaction between acetylcholine and epinephrine involves an antagonism at an intracellular level.

Role of calcium in caffeine-norepinephrine interactions in cardiac Purkinje fibers

1989 ◽  
Vol 257 (1) ◽  
pp. H226-H237 ◽  
Author(s):  
H. Satoh ◽  
M. Vassalle
Keyword(s):  
Calcium Concentration ◽  
Iodoacetic Acid ◽  
Slow Inward Current ◽  
Extracellular Potassium ◽  
Purkinje Fibers ◽  
Extracellular Potassium Concentration ◽  
Cardiac Purkinje Fibers ◽  
Ca Uptake

Caffeine-norepinephrine interactions were studied in canine cardiac Purkinje fibers perfused in vitro. Caffeine (0.5-1 mM) or theophylline (0.5-1 mM) increased and then decreased contractile force in the absence and presence of 0.5-10 microM norepinephrine (NE) [in high extracellular calcium concentration ([Ca]o) caffeine only decreases force]. Occasionally, caffeine only decreased force in the presence of NE. In the presence of NE and 12 mM (sometimes even 4 mM) extracellular potassium concentration, caffeine did not decrease force below the precaffeine level. Reciprocally, in 0.5-2 mM caffeine NE increased force, although less than in the absence of caffeine. Even in 9 mM caffeine, NE increased force but slowed the final phase three repolarization of the action potential. Both NE and 8.1 mM [Ca]o increased force, but NE decreased force in the presence of high [Ca]o. In NE and propranolol (or propranolol alone), caffeine only increased force, whereas it had the usual effects in the presence of methoxamine or phenotolamine. In the presence of iodoacetic acid and 2-deoxy-D-glucose, NE caused contracture and caffeine exaggerated it. In contrast, in NE and 2 mM Mn, caffeine only increased force. It is concluded that initially NE diminishes the cytoplasmic calcium overload induced by caffeine (by promoting Ca uptake into the sarcoplasmic reticulum) and subsequently enhances it (by increasing the slow inward current).

Role of chloride ions in cardiac action and pacemaker potentials

1963 ◽  
Vol 205 (3) ◽  
pp. 567-575 ◽  
Author(s):  
Walmor Carlos de Mello
Keyword(s):  
Chloride Ions ◽  
Resting Potential ◽  
Appreciable Amount ◽  
Purkinje Fibers ◽  
Atrial Muscle ◽  
Diastolic Depolarization ◽  
Anionic Permeability ◽  
Pacemaker Potentials ◽  
Bromide Solutions

Evidence is presented that chloride ions are able to carry an appreciable amount of electric charge through the membrane of atrial muscle fibers, Purkinje fibers, and fibers of the S-A nodal pacemaker. An increase in the slope of diastolic depolarization of pacemaker fibers was recorded when Cl– was replaced by larger anions (sulfate) in the external medium. The rate of repolarization decreased when larger anions were substituted for chloride ions, and it was increased in nitrate or bromide solutions. The anionic permeability of the cell membrane of S-A node, atrial muscle, and Purkinje fibers seems to follow the series: NO3– > Br– > Cl– > CH3COO– > SO4= Evidence is presented that chloride ions contribute to diastolic depolarization of pacemaker fibers. The K+ electrode properties of resting membrane of fibers of the S-A node were investigated at low and at constant extracellular Cl– concentration. It was found that above 16 mm K2SO4 there is agreement between the resting potential and Ek. Below this K+ concentration a deviation of the resting potential from the line for a K+ electrode was observed. Determinations of the Cl– content and of volume changes support the idea that the membrane of fibers of the S-A node and atrial muscle is permeable to Cl– and to K+ ions.

Monophasic action potential recordings in response to graded hyperkalemia in dogs

1989 ◽  
Vol 256 (4) ◽  
pp. H956-H961
Author(s):  
P. M. Sutton ◽  
P. Taggart ◽  
D. W. Spear ◽  
H. F. Drake ◽  
R. H. Swanton ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Regional Differences ◽  
Monophasic Action Potential ◽  
Extracellular Potassium ◽  
Activation Time ◽  
Biphasic Response ◽  
The Difference ◽  
Alpha Chloralose

Recent interest in sudden cardiac death during exercise in normal healthy people has highlighted the possible role of swings of extracellular potassium in arrhythmogenesis in conditions other than ischemia. Regional differences in action potential duration and conduction may be important. We have recorded monophasic action potentials (MAPs) from the endocardium and epicardium in nine open-chest dogs during graded intravenous infusion of potassium up to a plasma level of 9 mM. The animals were anesthetized with alpha-chloralose and urethan. Continuous, online arterial potassium monitoring was employed. MAP duration showed a biphasic response with initial shortening up to 7 mM, which tended to be more obvious on the epicardium. Regional activation time was measured as the difference between the onset of depolarization of the endocardial and epicardial MAP. Regional activation time also showed a biphasic response with initial shortening and subsequent delay. The QRS width of the scalar lead II electrocardiogram also showed biphasic changes, and the T wave amplitude progressively decreased. Our results suggest that regional differences in repolarization time may develop in the nonischemic myocardium in response to increased extracellular potassium levels mainly as a result of local changes in regional activation time rather than as a result of a direct effect on action potential duration.

Acetylcholine increases intracellular sodium activity in sheep cardiac Purkinje fibers

1989 ◽  
Vol 256 (5) ◽  
pp. H1407-H1416
Author(s):  
G. Iacono ◽  
M. Vassalle
Keyword(s):  
Action Potential ◽  
Spontaneous Activity ◽  
Sodium Pump ◽  
Contractile Force ◽  
Intracellular Sodium ◽  
Resting Potential ◽  
Purkinje Fibers ◽  
Transmembrane Potentials ◽  
Sodium Activity ◽  
Cardiac Purkinje Fibers

The action of acetylcholine (ACh) on intracellular sodium activity (alpha iNa) was studied in sheep Purkinje fibers by means of a Na+-selective microelectrode technique while transmembrane potentials and contractile force were simultaneously recorded. In quiescent fibers, 10(-4) to 10(-5) M ACh shifted the resting potential to less negative values and increased alpha iNa from 5.57 +/- 0.21 to 6.45 +/- 0.35 mM (+15.8%, P less than 0.005). In other experiments, ACh induced a depolarization that initiated spontaneous activity. In fibers driven at 60 beats/min, ACh prolonged the action potential, increased alpha iNa from 7.98 +/- 0.15 to 9.36 +/- 0.3 mM (+17.29%, P less than 0.005), and increased contractile force. Norepinephrine (10(-5) to 10(-6) M) increased contractile force and decreased alpha iNa, but in its presence ACh still increased force and alpha iNa and vice versa. Strophanthidin (10(-4) M) increased alpha iNa, and 3 x 10(-6) M propranolol and 10(-6) M atropine decreased alpha iNa. Both strophanthidin and atropine (but not propranolol) prevented the increase in alpha iNa by ACh. It is concluded that the ACh increases alpha iNa and contractile force through the inhibition of the sodium pump and that these actions are due to the activation of the muscarinic receptor and not to endogenously released norepinephrine.

An electrophysiological study of single somatosensory neurons in rat granular cortex serving the limbs: a laminar analysis

1988 ◽  
Vol 60 (2) ◽  
pp. 703-724 ◽  
Author(s):  
R. W. Dykes ◽  
Y. Lamour
Keyword(s):  
Action Potential ◽  
Spontaneous Activity ◽  
Pyramidal Tract ◽  
Electrophysiological Study ◽  
Receptive Fields ◽  
Discharge Frequency ◽  
Spontaneous Discharge ◽  
Sprague Dawley ◽  
Potential Shape ◽  
Pyramidal Tract Neurons

1. Recordings were made from 545 neurons in somatosensory granular cortex of anesthetized Sprague-Dawley rats. Of this sample, 32% were active spontaneously. Active neurons were not distributed uniformly throughout cortex but were most common in layer V. The highest mean spontaneous discharge frequency also was found in this layer. Cells with the lowest rates of spontaneous activity were located immediately above and below. One subset of spontaneously active neurons was characterized by an unusually high discharge frequency modulated by somatic stimulation. 2. Only 25.8% of the 534 neurons tested in granular cortex could be activated by somatic stimuli. Only 9.4% had cutaneous receptive fields, and 2.4% received deep inputs. The remainder (14.0%) were driven by higher intensity stimuli and could not be classified unequivocally as either cutaneous or deep. The 50 neurons with cutaneous receptive fields were located in the middle third of the cortex, and those with the largest receptive fields were found most superficially. Neurons driven by somatic stimuli were found most frequently in layer Vb, where 44.5% of the sample confirmed histologically to be in layer Vb could be excited. 3. The large proportion of neurons lacking demonstrable somatic inputs was attributed to the use of iontophoretically administered glutamate, which allowed the detection of many unresponsive neurons. This proportion was not reduced by the use of nitrous oxide and halothane as an anesthetic. 4. Neurons activated only by deep inputs were found on the medial and rostral edge of the hindlimb granular cortex, suggesting that deep and cutaneous inputs may be segregated in this species. 5. Electrical stimuli applied to the foot pads activated a sample of neurons differing from those driven by natural somatic stimuli in terms of depth, spontaneous activity, probability of somatic input, and probability of activation by the pyramidal tract. 6. Pyramidal tract neurons tended to be located in layer Vb, were active spontaneously, and had evidence of somatic inputs, although most required relatively intense stimuli to be excited. Other neurons activated synaptically from the pyramidal tract were located in the layers immediately above and below the pyramidal tract neurons. These cells were divided into two groups on the basis of action-potential latency, action-potential shape, and sensitivity to acetylcholine.

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