The use of a microcomputer to automate measurement of action potential duration for both transmembrane and monophasic action potentials

Background The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization. Methods The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters. Results Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected. Conclusions This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.

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Enhancement of GABAA receptor-mediated conductances induced by nerve injury in a subclass of sensory neurons

Journal of Neurophysiology ◽

10.1152/jn.1995.74.2.673 ◽

1995 ◽

Vol 74 (2) ◽

pp. 673-683 ◽

Cited By ~ 24

Author(s):

A. A. Oyelese ◽

D. L. Eng ◽

G. B. Richerson ◽

J. D. Kocsis

Keyword(s):

Action Potential ◽

Nerve Injury ◽

Action Potential Duration ◽

Action Potentials ◽

Resting Potential ◽

Drg Neurons ◽

Duration Of Action ◽

Whole Cell ◽

The Mean ◽

Large Neurons

1. The effects of axotomy on the electrophysiologic properties of adult rat dorsal root ganglion (DRG) neurons were studied to understand the changes in excitability induced by traumatic nerve injury. Nerve injury was induced in vivo by sciatic nerve ligation with distal nerve transection. Two to four weeks after nerve ligation, a time when a neuroma forms, lumbar (L4 and L5) DRG neurons were removed and placed in short-term tissue culture. Whole cell patch-clamp recordings were made 5–24 h after plating. 2. DRG neurons were grouped into large (43–65 microns)-, medium (34–42 microns)-, and small (20–32 microns)- sized classes. Large neurons had short duration action potentials with approximately 60% having inflections on the falling phase of their action potentials. In contrast, action potentials of medium and small neurons were longer in duration and approximately 68% had inflections. 3. Pressure microejection of gamma-aminobutyric acid (GABA, 100 microM) or muscimol (100 microM) onto voltage-clamped DRG neurons elicited a rapidly desensitizing inward current that was blocked by 200 microM bicuculline. To measure the peak conductance induced by GABA or muscimol, neurons were voltage-clamped at a holding potential of -60 mV, and pulses to -80 mV and -100 mV were applied at a rate of 2.5 or 5 Hz during drug application. Slope conductances were calculated from plots of whole cell current measured at each of these potentials. 4. GABA-induced currents and conductances of control DRG neurons increased progressively with cell diameter. The mean GABA conductance was 36 +/- 10 nS (mean +/- SE) in small neurons, 124 +/- 21 nS in medium neurons, and 527 +/- 65 nS in large neurons. 5. After axotomy, medium neurons had significantly larger GABA-induced conductances compared with medium control neurons (390 +/- 50 vs. 124 +/- 21; P < 0.001). The increase in GABA conductance of medium neurons was associated with a decrease in duration of action potentials. In contrast, small neurons had no change in GABA conductance or action potential duration after ligation. The GABA conductance of large control neurons was highly variable, and ligation resulted in an increase that was significant only for neurons > 50 microns. The mean action potential duration in large neurons was not significantly changed, but neurons with inflections on the falling phase of the action potential were less common after ligation. There was no difference in resting potential or input resistance between control and ligated groups, except that the resting potential was less negative in small cells after axotomy.(ABSTRACT TRUNCATED AT 400 WORDS)

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Changes in ventricular repolarization during acidosis and low-flow ischemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.275.2.h551 ◽

1998 ◽

Vol 275 (2) ◽

pp. H551-H561 ◽

Cited By ~ 16

Author(s):

Hugh W. L. Bethell ◽

Jamie I. Vandenberg ◽

Gerry A. Smith ◽

Andrew A. Grace

Keyword(s):

Action Potential ◽

Action Potentials ◽

Respiratory Acidosis ◽

Control Flow ◽

Low Flow ◽

Channel Blockers ◽

Monophasic Action Potentials ◽

Ferret Heart ◽

Action Potential Repolarization ◽

Intact Heart

Myocardial ischemia, primarily a metabolic insult, is also defined by altered cardiac mechanical and electrical activity. We have investigated the metabolic contributions to the electrophysiological changes during low-flow ischemia (7.5% of the control flow) using31P NMR spectroscopy to monitor metabolic parameters, suction electrodes to study epicardial monophasic action potentials, and 86Rb as a tracer for K+-equivalent efflux during low-flow ischemia in the Langendorff-perfused ferret heart. Shortening of the action potential duration at 90% repolarization (APD90) was most marked between 1 and 5 min after induction of ischemia, at which time it shortened from 261 ± 4 to 213 ± 8 ms. The period of marked APD90 shortening was accompanied by a fivefold increase in the rate of86Rb efflux, both of which were inhibited by the ATP-sensitive K+(KATP)-channel blockers glibenclamide and 5-hydroxydecanoate (5-HD), as well as by a significant fall in intracellular pH (pHi) from 7.14 ± 0.02 to 6.83 ± 0.03 but no change in intracellular ATP concentration ([ATP]i). We therefore investigated whether a fall in pHi could be the metabolic change responsible for modulating cardiac KATP channel activity in the intact heart during ischemia. Both metabolic (30 mM lactate added to extracellular solution) and respiratory ([Formula: see text] increased to 15%) acidosis caused an initial lengthening of APD90 to 112 ± 1.5 and 113 ± 0.9%, respectively, followed by shortening during continued acidosis to 106 ± 1.2 and 106 ± 1.4%, respectively. The shortening of APD90 during continued acidosis was inhibited by glibenclamide, consistent with acidosis causing activation of KATP channels at normal [ATP]i. The similar responses to metabolic (induced by adding either l- or d-lactate) and respiratory acidosis suggest that lactate has no independent metabolic effect on action potential repolarization.

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Detachable glass microelectrodes for recording action potentials in active moving organs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00741.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. H1248-H1259 ◽

Cited By ~ 3

Author(s):

Mladen Barbic ◽

Angel Moreno ◽

Tim D. Harris ◽

Matthew W. Kay

Keyword(s):

Action Potential ◽

Action Potential Duration ◽

Action Potentials ◽

Ischemia Reperfusion ◽

Cellular Level ◽

High Temporal Resolution ◽

Physiological Relevance ◽

Glass Micropipette ◽

Multiple Cells

Here, we describe new detachable floating glass micropipette electrode devices that provide targeted action potential recordings in active moving organs without requiring constant mechanical constraint or pharmacological inhibition of tissue motion. The technology is based on the concept of a glass micropipette electrode that is held firmly during cell targeting and intracellular insertion, after which a 100-µg glass microelectrode, a “microdevice,” is gently released to remain within the moving organ. The microdevices provide long-term recordings of action potentials, even during millimeter-scale movement of tissue in which the device is embedded. We demonstrate two different glass micropipette electrode holding and detachment designs appropriate for the heart (sharp glass microdevices for cardiac myocytes in rats, guinea pigs, and humans) and the brain (patch glass microdevices for neurons in rats). We explain how microdevices enable measurements of multiple cells within a moving organ that are typically difficult with other technologies. Using sharp microdevices, action potential duration was monitored continuously for 15 min in unconstrained perfused hearts during global ischemia-reperfusion, providing beat-to-beat measurements of changes in action potential duration. Action potentials from neurons in the hippocampus of anesthetized rats were measured with patch microdevices, which provided stable base potentials during long-term recordings. Our results demonstrate that detachable microdevices are an elegant and robust tool to record electrical activity with high temporal resolution and cellular level localization without disturbing the physiological working conditions of the organ. NEW & NOTEWORTHY Cellular action potential measurements within tissue using glass micropipette electrodes usually require tissue immobilization, potentially influencing the physiological relevance of the measurement. Here, we addressed this limitation with novel 100-µg detachable glass microelectrodes that can be precisely positioned to provide long-term measurements of action potential duration during unconstrained tissue movement.

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Effects of moderate hypoxia on premature action potentials of rabbit papillary muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-095 ◽

1984 ◽

Vol 62 (5) ◽

pp. 596-599

Author(s):

Julio Alvarez ◽

Francisco Dorticós ◽

Jesús Morlans

Keyword(s):

Action Potential ◽

Action Potential Duration ◽

Action Potentials ◽

Potassium Current ◽

Maximum Rate ◽

Resting Potential ◽

Papillary Muscles ◽

Premature Response ◽

Coupling Interval ◽

Control Response

Experiments were performed to study the effects of hypoxia on the characteristics of premature action potentials of rabbit papillary muscles. At normal resting potential, the duration of the premature action potential at the shortest coupling intervals was always greater than that of the control response. As the coupling interval was increased beyond 150 ms, the duration of the premature action potential regained control values. In cells depolarized to −70 mV by KCl, early lengthening of the premature response was attenuated. After 60 min of hypoxia, recovery of action potential duration at normal and reduced resting potentials was accelerated. The maximum rate of depolarization and its reactivation time constant were not affected by 60 min of hypoxia. It is suggested that intracellular free Ca is important in the control of action potential duration via the outward background potassium current.

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Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

Journal of Neurophysiology ◽

10.1152/jn.01107.2010 ◽

2011 ◽

Vol 106 (1) ◽

pp. 144-152 ◽

Cited By ~ 15

Author(s):

Yu Liu ◽

Iaroslav Savtchouk ◽

Shoana Acharjee ◽

Siqiong June Liu

Keyword(s):

Potassium Channels ◽

Action Potential ◽

Action Potential Duration ◽

Action Potentials ◽

Channel Blocker ◽

Stellate Cells ◽

Bk Channels ◽

Bk Channel ◽

K Channel ◽

Duration Of Action

Many fast-spiking inhibitory interneurons, including cerebellar stellate cells, fire brief action potentials and express α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors (AMPAR) that are permeable to Ca2+ and do not contain the GluR2 subunit. In a recent study, we found that increasing action potential duration promotes GluR2 gene transcription in stellate cells. We have now tested the prediction that activation of potassium channels that control the duration of action potentials can suppress the expression of GluR2-containing AMPARs at stellate cell synapses. We find that large-conductance Ca2+-activated potassium (BK) channels mediate a large proportion of the depolarization-evoked noninactivating potassium current in stellate cells. Pharmacological blockade of BK channels prolonged the action potential duration in postsynaptic stellate cells and altered synaptic AMPAR subtype from GluR2-lacking to GluR2-containing Ca2+-impermeable AMPARs. An L-type channel blocker abolished an increase in Ca2+ entry that was associated with spike broadening and also prevented the BK channel blocker-induced switch in AMPAR phenotype. Thus blocking BK potassium channels prolongs the action potential duration and increases the expression of GluR2-containing receptors at the synapse by enhancing Ca2+ entry in cerebellar stellate cells.

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COMPUTING CARDIAC RECOVERY MAPS FROM ELECTROGRAMS AND MONOPHASIC ACTION POTENTIALS UNDER HETEROGENEOUS AND ISCHEMIC CONDITIONS

Mathematical Models and Methods in Applied Sciences ◽

10.1142/s021820251000457x ◽

2010 ◽

Vol 20 (07) ◽

pp. 1089-1127 ◽

Cited By ~ 16

Author(s):

SIMONE SCACCHI ◽

PIERO COLLI FRANZONE ◽

LUCA F. PAVARINO ◽

B. TACCARDI

Keyword(s):

Action Potential ◽

Action Potentials ◽

Correlation Coefficients ◽

Recovery Phase ◽

Computing Power ◽

Pathological Conditions ◽

Monophasic Action Potentials ◽

Recovery Times ◽

3D Sequence ◽

Unipolar Electrograms

The currently available techniques to investigate the 3D sequence of activation and recovery in the cardiac atria and ventricles, with high spatial resolution, are based on extracellular electrical recordings. The goal of the present work is to provide an extensive quantitative analysis of the accuracy level of commonly used recovery time (RT) markers, under heterogeneous and pathological conditions of the myocardial tissue, such as myocardial ischemia. A widely used technique is based on unipolar electrograms (EGs); an alternative technique is based on hybrid monophasic action potentials (HMAPs), obtained as the potential difference between a permanently depolarized site and an exploring site. The RT markers derived from EGs and HMAPs are compared with two transmembrane action potential (TAP) markers considered here as gold standards for the fastest and final recovery phase, respectively. The analysis is based on 3D numerical simulations of the action potential propagation in anisotropic and insulated cardiac blocks, modeled by the Bidomain system coupled with the Luo–Rudy I membrane model. These demanding simulations have been made possible by recent advances in computing power and multilevel Bidomain solvers. The results show that the extracellular RT markers considered are reliable estimates of the gold standard TAP markers, with low relative mean discrepancies and high correlation coefficients. We also investigate the capability of the markers to discriminate different transmural dispersions of recovery times and action potential durations. In some specific pathological cases when the EG markers fail, the HMAP markers may offer reliable alternatives.

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Myocardial Depressant Effects of Sevoflurane

Anesthesiology ◽

10.1097/00000542-199605000-00019 ◽

1996 ◽

Vol 84 (5) ◽

pp. 1166-1176 ◽

Cited By ~ 76

Author(s):

Wyun Kon Park ◽

Joseph J. Pancrazio ◽

Chang Kook Suh ◽

Carl III Lynch

Keyword(s):

Sarcoplasmic Reticulum ◽

Guinea Pig ◽

Action Potential ◽

Papillary Muscle ◽

Action Potential Duration ◽

Action Potentials ◽

Peak Force ◽

Rapid Cooling ◽

K Current ◽

Slow Action Potentials

Background The effects of anesthetic concentrations of sevoflurane were studied in isolated myocardial tissue to delineate the mechanisms by which cardiac function is altered. Methods Isometric force of isolated guinea pig ventricular papillary muscle was studied at 37 degrees C in normal and 26 mM K+ Tyrode's solution at various stimulation rates. Normal and slow action potentials were evaluated using conventional microelectrodes. Effects of sevoflurane on sarcoplasmic reticulum function in situ were also evaluated by its effect on rapid cooling contractures, which are known to activate Ca2+ release from the sarcoplasmic reticulum, and on concentrations of rat papillary muscle. Finally, Ca2+ and K+ currents of isolated guinea pig ventricular myocytes were examined using the whole-cell patch clamp technique. Results Sevoflurane equivalent to 1.4% and 2.8% depressed guinea pig myocardial contractions to approximately 85 and approximately 65% of control, respectively, although the maximum rate of force development at 2 or 3 Hz and force in rat myocardium after rest showed less depression. In the partially depolarized, beta-adrenergically stimulated myocardium, sevoflurane selectively depressed late peak force without changing early peak force, whereas it virtually abolished rapid cooling contractures. Sevoflurane did not alter the peak amplitude or maximum depolarization rate of normal and slow action potentials, but action potential duration was significantly prolonged. In isolated guinea pig myocytes at room temperature, 0.7 mM sevoflurane (equivalent to 3.4%) depressed peak Ca2+ current by approximately 25% and increased the apparent rate of inactivation. The delayed outward K+ current was markedly depressed, but the inwardly rectifying K+ current was only slightly affected by 0.35 mM sevoflurane. Conclusions These results suggest that the direct myocardial depressant effects of sevoflurane are similar to those previously described for isoflurane. The rapid initial release of Ca2+ from the sarcoplasmic reticulum is not markedly decreased, although certain release pathway, specifically those induced by rapid cooling, appear to be depressed. Contractile depression may be partly related to the depression of Ca2+ influx through the cardiac membrane. The major electrophysiologic effect of sevoflurane seems to be a depression of the delayed outward K+ current, which appears to underlie the increased action potential duration.

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