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PubMed1995

Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons.

The site of action potential initiation in substantia nigra neurons was investigated by using simultaneous somatic and dendritic whole-cell recording in brain slices. In many dopamine neurons, action potentials were observed first at the dendritic recording site. Anatomical reconstruction showed that in these neurons, the axon emerged from the dendrite from which the recording had been made. Action potentials showed little attention in the dendritic tree, which in dopamine neurons was shown to be due to recruitment of dendritic sodium channels and may be related to the dendritic release of dopamine. We conclude that in substantia nigra neurons, the site of action potential initiation, and thus the final site of synaptic integration, is in the axon. As the axon can originate from a dendrite, up to 240 microns away from the soma, synaptic input to the axon-bearing dendrite may be privileged with respect to its ability to influence action potential initiation.

Action Potentials↗

PubMed1995

Transient prolongation of ventricular action potential duration after metabolic inhibition.

Transient prolongation of the action potential duration was observed in canine ventricular muscle during the reoxygenation period following metabolic inhibition. We investigated the effects of verapamil, lanthanum (La3+), and hexamethyleneamiloride (HMA) on the recovery time course of the action potential and its rebound prolongation. The time course of the intracellular resistivity was estimated from the conduction velocity and electrograms. The action potentials of canine left ventricular trabeculae were recorded by the conventional microelectrode technique. After a control tracing was obtained, the preparation was perfused with a hypoxic, acidic solution for 20 min and then reoxygenated with regular Tyrode's solution. After reoxygenation, action potential prolongation exceeding the control value by 21.0 +/- 7.3% was observed depending on the degree of metabolic inhibition. Verapamil depressed the rebound prolongation when it was added before the start of metabolic inhibition, but not when added after reoxygenation was started. La3+ and HMA depressed the rebound phenomenon. Intracellular resistivity was increased during metabolic inhibition, but showed no significant changes during the period of action potential prolongation. It was concluded that the rebound action potential prolongation was related to the accumulation of intracellular Ca2+ during metabolic inhibition. Other ions, such as Na+ and H+ may also contribute to the phenomenon by modulating outward currents.

Action Potentials↗

PubMed1985

Frequency-dependent action potential prolongation in Aplysia pleural sensory neurones.

The effects of repetitive activity on action-potential shape in Aplysia californica pleural sensory cells are described. Action potentials were evoked by intracellular current injection at frequencies between 7.41 and 0.2 Hz. In contrast to other molluscan neurons having brief action potentials, it was found that at these firing rates the normally brief action potential develops a prominent shoulder or plateau during the repolarization phase. Higher stimulus rates broaden the action potential more rapidly and to a greater extent than lower stimulus rates. Inactivation is slow relative to activation; effects of 3-s 6-Hz trains are detectable after 1 min rest. The amplitude of the plateau voltage reaches a maximum of 50-70 mV at the highest stimulus rates tested. Frequency-dependent increases in action-potential duration measured at half-amplitude normally range between 6 and 15 ms. Cadmium, at concentrations between 0.05 and 0.5 mM, antagonizes frequency-dependent broadening. The increases in duration induced by repetitive activity are more sensitive to cadmium than are the increases in plateau amplitude. Tetraethylammonium, at concentrations between 0.5 and 10 mM, slightly increases the duration and amplitude of single action potentials. During repetitive activity at high stimulus rates the maximum duration and rate of broadening are both increased but the amplitude of the plateau potential is not affected by these tetraethylammonium concentrations. Above 10 mM, tetraethylammonium greatly increases the duration and amplitude of single action potentials as well as the rates of action-potential duration and amplitude increase during repetitive activity. These high tetraethylammonium concentrations also cause the normally smoothly increasing duration and amplitude to reach a maximum value early in a train and then decline slowly during the remainder of the train. The consequences of frequency-dependent spike broadening in these neurons have not yet been investigated but it is clear from these data that repetitive activity in these cells will augment calcium entry and that this increased calcium entry has a complex but predictable dependence on the duration of, and firing rate within, an afferent volley. Because these cells are involved in important adaptive behaviour it is inferred that these behaviours will be complexly affected by the intensity and duration of the stimulation of the receptive fields of the pleural sensory neurons.

Action Potentials↗

PubMed2006

Can optical recordings of membrane potential be used to screen for drug-induced action potential prolongation in single cardiac myocytes?

INTRODUCTION: Potential-sensitive dyes have primarily been used to optically record action potentials (APs) in whole heart tissue. Using these dyes to record drug-induced changes in AP morphology of isolated cardiac myocytes could provide an opportunity to develop medium throughout assays for the pharmaceutical industry. Ideally, this requires that the dye has a consistent and rapid response to membrane potential, is insensitive to movement, and does not itself affect AP morphology. MATERIALS AND METHODS: We recorded the AP from isolated adult guinea-pig ventricular myocytes optically using di-8-ANEPPS in a single-excitation dual-emission ratiometric system, either separately in electrically field stimulated myocytes, or simultaneously with an electrical AP recorded with a patch electrode in the whole-cell bridge mode. The ratio of di-8-ANEPPS fluorescence signal was calibrated against membrane potential using a switch-clamp to voltage clamp the myocyte. RESULTS: Our data show that the ratio of the optical signals emitted at 560/620 nm is linearly related to voltage over the voltage range of an AP, producing a change in ratio of 7.5% per 100 mV, is unaffected by cell movement and is identical to the AP recorded simultaneously with a patch electrode. However, the APD90 recorded optically in myocytes loaded with di-8-ANEPPS was significantly longer than in unloaded myocytes recorded with a patch electrode (355.6+/-13.5 vs. 296.2+/-16.2 ms; p<0.01). Despite this effect, the apparent IC50 for cisapride, which prolongs the AP by blocking IKr, was not significantly different whether determined optically or with a patch electrode (91+/-46 vs. 81+/-20 nM). DISCUSSION: These data show that the optical AP recorded ratiometrically using di-8-ANEPPS from a single ventricular myocyte accurately follows the action potential morphology. This technique can be used to estimate the AP prolonging effects of a compound, although di-8-ANEPPS itself prolongs APD90. Optical dyes require less technical skills and are less invasive than conventional electrophysiological techniques and, when coupled to ventricular myocytes, decreases animal usage and facilitates higher throughput assays.

Action Potentials↗

PubMedDate not supplied

Thresholds of intracranially recorded auditory field potentials in the pigeon compared with compound action potential thresholds.

The compound action potential (CAP) thresholds provide a reliable indicator for cochlear functional integrity during experimentation in birds as well as in mammals. However, if experimental manipulations are necessary in the middle ear/inner ear spaces, the round window electrodes are often inconvenient. In search for an alternative for CAP recordings, intracranial recordings of acoustically evoked field potentials from the nucleus angularis/magnocellularis were made in pigeons using stereotactically placed electrodes. The responses were compared with those recorded from intracranial surface electrodes placed on the dura mater and compared with CAP responses recorded from the round window. The field potentials recorded from the nucleus angularis/magnocellularis contain a significant contribution from the auditory nerve, as large in amplitude as the CAP recorded at the round window. The recordings from the intracranial surface electrodes were noisier and the contribution from the auditory nerve was too small to be used as a fast monitor of the condition of the inner ear. Threshold curves as a function of frequency could be determined with an automated method from the nucleus angularis/magnocellularis with the same sensitivity and accuracy as from the round window CAP within a few minutes. These results demonstrate that stereotactic recordings of field potentials from the nucleus magnocellularis/angularis region are a suitable alternative to reliably monitor the condition of the inner ear when round window electrodes cannot be used.

Animals↗

PubMed1990

Influence of electrogenic Na/Ca exchange on the action potential in human heart muscle.

STUDY OBJECTIVE: The plateau of the action potential in heart muscle is largely due to the inward Ca2+ current, ica; however, Ca2+ extrusion via Na+/Ca2+ exchange may also generate a significant current, ina/ca. The aim was to assess the influence of ina/ca on the action potential in isolated human heart muscle. DESIGN: Action potentials and force of isometric contractions were recorded in ventricular trabeculae. The muscle was subjected to various stimulus patterns, Ca2+ antagonists, and variations in the ionic composition of the extracellular medium. PATIENTS: From 49 patients, aged 0.5 to 14 years, small right ventricular trabeculae were obtained during open heart surgery. The operations concerned corrections of ventricular septal defects. Data presented in this paper were from nine preparations in which action potentials were recorded during several hours. MEASUREMENTS AND MAIN RESULTS: The results confirmed that: (1) the amplitude of the early part of the plateau was depressed by low [Ca2+] and by Ca2+ antagonists, showing that ica dominates this early part; and (2) that low [Na2+] and post-extrasystolic potentiation also depressed the early component of the plateau of the action potential, which can be explained by inactivation of ica due to increased levels of intracellular Ca2+. A novel observation was that post-extrasystolic potentiation led to an increase in action potential duration (APD). An explanation is that the potentiated contraction follows from an increased amount of intracellular Ca2+ which also activates an inward current, possibly ina/ca. This assumption is strengthened by the finding that lengthening of APD after extrasystoles was abolished: (a) at low [Ca2+], ie, when force was small and there was little Ca2+ to be extruded; and (b) at low [Na+], ie, when force was large but the driving force of the Na+ gradient for extrusion of Ca2+ was small. CONCLUSIONS: The early part of the plateau is dominated by ica, whereas ina/ca is relatively more important during the later part, and tends to lengthen the action potential.

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PubMed2001

Simple techniques suitable for student use to record action potentials from the frog heart.

Demonstrating action potentials during class experiments is very educational for science students. It is not easy, however, to obtain a stable intracellular recording of action potentials from the conventionally used skeletal muscle cells, because the tip of a glass microelectrode often comes out or breaks due to muscle contraction. Here, I present a much simpler recording method using a flexible polyethylene electrode with a wide orifice (approximately 1 mm) for a bullfrog heart beating on automaticity. Extracellular recordings of action potentials (electrocardiogram) can be obtained by placing an electrode on the cardiac surface, and transmembrane potentials can be obtained by rupturing the membrane with negative pressure, i.e., whole cell configuration. Once attached to the heart by suction, the polyethylene electrode does not easily come off during contraction of the heart. Perfusion of the heart via the postcaval vein offers us opportunities for observing the effects of either changing ionic compositions of solutions or applying drugs. The techniques shown here provide a simple and convenient way to perform a variety of class experiments.

Action Potentials↗

PubMed2004

[Effects of Evan Blue on perfused dimension display and rabbit left ventricular action potential].

OBJECTIVE: Simultaneous recording of transmembrane action potential at endocardium, midcardium and epicardium and transmural ECG in arterially perfused left ventricular preparation is a new method for researching into the mechanism about ventricular arrhythmia, and in this connection, how to distinguish the perfused area plays a key role in keeping preparations under normal condition. This study is aimed to evaluate the effects of Evan Blue on the displaying of the perfused area and on the characters of transmembrane action potential of the arterially perfused left ventricular preparations. METHODS: Rabbit left ventricular wedge preparations were perfused with Tyrode solution continuously via left circumflex, and the action potential of endocardium, midmyocardium, epicardium or transmural electrocardiogram were recorded simultaneously. The action poatential duration (APD), transmural dispersion of repolarization (TDR) or QT intervals were compared and the color variation of the preparations were studied before and 30 min after perfusion with Evan Blue. RESULTS: Under the basic stimulatory cycle length of 1000, 2000, 4000 ms, there was no significant difference of APD in the same transmural layer or TDR before and after Evan Blue perfusion (P<0.01), but APD or TDR stimulated at basic cycle length of 1000-4000 ms were all higher than those recorded at 500 ms (P<0.01); APDs of endocardium were much longer than those of epicardium or midmyocardium (P<0.01); there was no significant difference in APD, TDR and QT intervals before and after Evan Blue perfusion (P>0.05). No premature ventricular contractions and ventricular tachycardia happened during the experiments. CONCLUSION: Evan Blue can be used as a marker to identify the perfused area.

Action Potentials↗

PubMed2003

Effect of sotalol and acute ventricular dilatation on action potential duration and dispersion of repolarization after defibrillation shocks.

Ventricular dilatation shortens action potential duration and increases the defibrillation threshold, whereas sotalol prolongs action potential duration and may decrease the defibrillation threshold. Whether these action potential changes remain after defibrillation shocks, and how they relate to defibrillation success, is not known. In this study, eight monophasic action potentials were recorded simultaneously during electrical defibrillation (shock strength: 20%-200% of the defibrillation threshold) in 16 normal and acutely dilated isolated rabbit hearts at baseline and after addition of sotalol (2 x 10-5 M). Post-shock action potential duration (PS-APD) and dispersion of PS-APD [Disp(PS-APD)] of monophasic action potentials were analyzed after 322 defibrillation shocks at different repolarization levels and related to defibrillation success. Acute ventricular dilatation shortened PS-APD, whereas sotalol prolonged PS-APD. Successful defibrillation was associated with lower Disp(PS-APD) at all repolarization levels in the normal and dilated heart at baseline and with sotalol (mean difference: 33%-46%, all P < 0.005). Minimal PS-APD was longer (mean difference: 5%-11%), while maximal PS-APD was shorter (mean difference: 2%-16%) after successful defibrillation shocks than after failing defibrillation shocks. Therefore, sotalol prolongs action potential duration after defibrillation shocks. Synchronization of repolarization, caused by both prolongation of short PS-APD and shortening of long PS-APD, is associated with successful defibrillation in the normal, acutely dilated, and sotalol-treated heart.

Action Potentials↗

PubMed1964

SOME EFFECTS OF CALCIUM IONS ON THE ACTION POTENTIAL OF SINGLE NODES OF RANVIER.

Action potentials of single frog nerve fibers were recorded with the air-gap method in "low Ca" (0.26 mM) and "high Ca" (4.2 mM) solutions and compared to spikes in normal Ringer's (1.05 mM Ca). On increasing (Ca)(o) the action potentials became shorter, the "knee" during the falling phase as well as the threshold for abolition moved to internal potentials more positive, and the spike recovery during the relative refractory period was faster. Outward current pulses applied during an action potential affected its configuration more in low Ca than in high Ca. The onset of the delayed rectification (in the absence of Na) was found faster in high Ga. After-potentials during anelectrotonus declined more rapidly in high Ca than in low Ca. The results are compared primarily with the voltage-clamp analysis of Ca effects on squid axons and satisfactory qualitative agreement is reached.

Action Potentials↗

PubMed1984

Physiological properties of the electrically stimulated auditory nerve. I. Compound action potential recordings.

The electrically evoked compound action potential (CAP) of the auditory nerve exhibits two peaks, termed N0, at 350 microseconds latency, and N1, at 550 microseconds latency. At low stimulus intensities the CAP consists solely of the long latency N1 peak. As the stimulus strength is increased the higher threshold N0 appears. At high stimulus intensities N1 disappears and only the N0 component of the CAP remains. It is postulated that N1 represents action potentials propagated from the dendritic processes of the auditory neurons and that N0 represents action potentials initiated on the axons of these cells. The N1 peak exhibits anomalous refractory behavior which can be identified in the electrically evoked auditory brainstem response (EABR). That behavior may be useful diagnostically in assessing the extent of dendrite degeneration in cochlear implant candidates and users.

Action Potentials↗

PubMed1993

Effects of temperature on cycle length dependent changes and restitution of action potential duration in guinea pig ventricular muscle.

OBJECTIVE: The aim was to investigate the effects of temperature on cycle length dependent changes of action potential duration and on restitution of action potential duration. METHODS: Guinea pig papillary muscle action potentials were recorded using conventional microelectrode techniques. Action potential duration was measured at cycle lengths ranging from 500 to 2000 ms at both 27 degrees C and 37 degrees C. Restitution of action potential duration was determined by introducing an extra stimulus at progressively longer diastolic intervals from 40 to 9000 ms at pacing cycle lengths of 500, 1000, and 2000 ms. RESULTS: At 37 degrees C, action potential duration measured at 90% of repolarisation (APD90) during continuous pacing and the maximum value of APD90 achieved during restitution (APD90pl) decreased by 18(SEM 6) ms (n = 7) and 24(7) ms (n = 6), respectively, when pacing cycle length was reduced from 2000 to 500 ms. At 27 degrees C, the magnitude of the shortening of APD90 and APD90pl observed when pacing cycle length was similarly reduced was greater than at 37 degrees C, ie, 143(21) ms (n = 6) and 115(11) ms (n = 6), respectively. Thus the relation for restitution of action potential duration shifted downwards with reduction in pacing cycle length, and the magnitude of this shift was greater at 27 degrees C than at 37 degrees C. The difference between APD90 at the shortest diastolic interval (40 ms) and at diastolic interval of 100 ms (range of premature action potential durations) was much greater at 27 degrees C than at 37 degrees C at all three pacing cycle lengths. CONCLUSIONS: Reduction in temperature magnifies the cycle length dependent changes in action potential duration both during abrupt changes in cycle length, as with an extra stimulus, and during changes of steady state cycle length. This may indicate a greater dispersion of premature action potential durations during hypothermia, and hence predispose to hypothermia induced arrhythmias.

Action Potentials↗

PubMed1998

The significance of atrial monophasic action potentials for monitoring rat cardiac allograft rejection.

BACKGROUND: Changes in the monophasic action potential may be used for detecting early acute rejection in the transplanted rat heart. METHODS: Heterotopic heart transplantations were performed in allogeneic and syngeneic rats. During atrial pacing, monophasic action potentials were simultaneously recorded in the right atrium and ventricle of the transplanted hearts on postoperative days 1, 3, and 5. The amplitude and duration of monophasic action potentials, atrioventricular conduction time, and cardiac intervals were analyzed. Histopathologic examination for rejection was performed on postoperative days 1, 3, and 5. RESULTS: In the allogeneic group, monophasic action potential amplitude progressively decreased, and monophasic action potential duration gradually increased after heart transplantation in the atrium and ventricle. With rejection, the amplitude decreased to a greater extent, and monophasic action potential duration increased to a greater extent in the atrium than in the ventricle on day 3. The atrioventricular conduction time increased on day 5, but the cardiac interval did not change. An inverse correlation between histopathologic grade and the monophasic action potential amplitude, and a positive correlation between histopathologic grade and the monophasic action potential duration existed for both the atrium and ventricle. These electrophysiologic and histopathologic changes were not observed in the syngeneic group. CONCLUSIONS: We conclude that right atrial monophasic action potentials may be a useful and reliable indicator of early acute heart transplant rejection.

Acute Disease↗

PubMed1993

Conductances contributing to the action potential of Sternopygus electrocytes.

In Sternopygus macrurus, electrocyte action potential duration determines the electric organ discharge pulse duration. Since the electric organ discharge is a sexually-dimorphic behavior under the control of steroid hormones, and because electrocyte action potential durations can range from 3-14 ms, the electrocytes provide a unique opportunity to study how sex steroids regulate membrane excitability. In this study, the voltage-sensitive ionic currents of electrocytes were identified under current- and voltage-clamp as a prelude to further studies on their regulation by sex steroid hormones. Bath application of TTX completely abolished the spike and eliminated an inward current under voltage clamp, indicating that the action potential is due primarily to a sodium current. Calcium-free saline had no effect on spike waveform or voltage-clamp currents, indicating that neither calcium nor calcium-dependent currents contribute to the action potential. Application of potassium channel blocking agents, such as tetraethylammonium and cesium ions, caused changes in the spike which, together with voltage-clamp results, indicate the presence of two potassium currents: an inward rectifier and a classical delayed rectifier. In addition, these cells have a large, presumably voltage-insensitive, chloride current. Differences in one or more of these currents could be responsible for the range of action potential durations found in these cells and for the steroid-mediated changes in spike duration.

Action Potentials↗

PubMed1980

The spontaneous action potential of rabbit atrioventricular node cells.

The rabbit atrioventricular (A-V) node, with dimensions of approximately 5 X 3 mm was dissected into 15 small specimens (0.5 X 0.5 mm). A majority of the specimens continued to discharge spontaneous action potentials, the action potential configuration being almost identical in different specimens. The amplitude (98 mV) and the maximum rate of rise of the action potential (11 V/sec) were similar to those recorded from the intact A-V node (amplitude 98 mV, maximum rate of rise of action potential 12 V/sec). In these small specimens, the "resting membrane potential (-44 mV)" was approximately 20 mV less negative than that in the intact A-V node preparation (-62 mV) before the dissecting procedure. The spontaneous discharge in these small A-V node specimens was attributed to the low resting membrane potential. The small specimen became inexcitable under the effects of blockers of is, though TTX had no significant effect on the action potential. The after-hyperpolarization was observed after cessation of the depolarizing current pulse. It is concluded that the slow inward current and the slow kinetics of the outward current contribute to the generation of the spontaneous A-V node action potentials as in the sinoatrial node.

Action Potentials↗

PubMed1978

The calculated radial decline of the extracellular action potential compared with in situ measurements in the human brachial biceps.

Action potentials from 16 single muscle fibres were recorded with a multi-electrode from the human brachial biceps. Propagation velocity was calculated for 10 of the fibres, and the volume conduction at distances of 79, 152 and 251 micrometer, was measured for 6 of these fibres. The radial decline of the action potentials was calculated from the Fourier transform of the action potential at the origin, simulating the low-pass filter characteristics of the muscle tissue by sections of RC elements. A good agreement was found between the calculated data and the experimental data on the radial decline of the action potentials. The 90% attenuation radius of the action potential recorded with a 25 micrometer electrode, calculated for 16 action potentials, was derived from the volume conduction calculations. The average value found was 191 +/- 20 micrometer. A linear correlation was found between this radius and the peak spectral amplitude of the action potentials. Likewise, a linear correlation between the 90% attenuation radius and the propagation velocity of the fibres was confirmed.

Action Potentials↗

PubMed1996

Determination of nerve conduction velocity distribution from sampled compound action potential signals.

The sampled compound action potential (CAP) data sequence was expressed as the circular convolution of the delay sequence and the sampled single fiber action potential (SFAP) data sequence. An algorithm, based on Hirose's method [1], was then developed to separate the delay sequence from the sampled CAP data sequence, and the nerve conduction velocity distribution (NCVD) was consequently calculated from the delay sequence. The NCVD was found to be the product of the amplitude of the SFAP and the number of fibers. Simulations show that the estimated results were in good agreement with the calculated results. Experiments were performed on ten sciatic nerves from five bullfrogs (Rana pipens) using two independent variables: interelectrode distance and stimulus current strength. The results estimated from CAP's recorded under each condition reflect the corresponding feature of NCVD of the condition. The advantage of the technique is to provide detailed information about both slow and fast conducting fibers. This technique also offers the possibility to directly calculate the nerve fiber diameter distribution from the sampled CAP data sequences.

Action Potentials↗

PubMed1984

Action potential of isolated frog utricle.

The action potential of an isolated frog utricle was recorded using a suction electrode. The utricle was stimulated with iron sand which were spread evenly on the macula. A magnetic force was employed to induce the iron sand to depress the macula lightly. Integration of the action potential resulted in a phasic component, just as observed in the isolated semicircular canal potential (Harada et al., 1969). The amplitude of the utricular phasic component was liner to the logarithm of the stimulus intensity. Similar relationship was observed between the semicircular canal action potential and the stimulus (Harada & Hirata, 1981). Phasic on-response was invariably accompanied by an off-response. This suggests functional polarization of the utricle. It is already known that the macula is divided by the striola into two hair-cell groups having differing polarity. Since iron sand is spread evenly on the macula, all sensory cilia bend in one direction at the onset of the stimulus and one of the two cell groups evokes an on-response. At termination of the stimulus, sensory cells with the opposite polarity are stimulated, thus producing an off-response.

Action Potentials↗