Copyright © 2004, European Society of Cardiology
Biophysical basis for monophasic action potential
Gordon K. Moe Scholar, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501-1787, United States
* Corresponding author. Tel.: +1 315 735 5648; fax: +1 315 735 5648. Email address: ca{at}mmrl.edu
Received 14 December 2004; accepted 22 December 2004
We welcome Dr. Franz's comments relative to our recent publication dealing with the monophasic action potential (MAP) [1]. We agree and fully appreciate the fact that the Franz contact electrode technique has been successfully used for over 20 years by Dr. Franz and other investigators. This success stems from the fact that the two electrodes of the contact catheter are relatively close to each other so that their combined field of view is fairly localized. However, we do not agree that this success can be used as an argument against our conclusion that it is not the tip electrode that records the MAP. Our study investigated the physical principles behind the MAP recording. We started with a simple definition of voltage as the difference of potential between two points or two electrodes. To determine which of these two potentials carries time-dependent information, we placed the two electrodes at sites with different cellular activity and observed which activity is reflected in the MAP signal. The observations demonstrated in a very straightforward manner that the tip or inactivating electrode is not the recording electrode. This conclusion provides support for theories introduced as early as 1934 [2].
Response to specific comments:
The size of the canine left ventricular wedge preparation is typically between 2 x 1.5 x 0.9 cm and 3 x 2 x 1.5 cm. The schemes in Figs. 4 and 8 correctly depict the relative dimensions of the contact MAP catheter and the wedge preparation. Moreover, in the schematics shown in Figs. 5, 6 and 7, the catheter is larger than its actual dimension relative to the size of the wedge.
The pioneering study by Dower et al. [3], cited by Dr. Franz, was aimed at development of an intracellular recording technique. The authors recognized that microelectrodes with a small tip diameter (<6 µm) record intracellular signals while larger electrodes depolarize tissue and record extracellular (MAP) signal with much wider field of view and corresponding distortions (see last paragraph on page 38 in [3]). Therefore, it remains that tissue depolarized by injury, mechanical pressure or by KCl is electrically inactive, and no extracellular activity takes place at that site. We are not aware of a "consensus" that the MAP originates from the site of injury or KCl application site.
Contrary to the assertion made by Dr. Franz of an n=1 for each of our experiments, we repeated each experiment 4 to 10 times and indicated the number of repetitions in the corresponding figure legends. Our experiments were designed to answer a qualitative question: which site, inactivated or active, contributes predominantly to the recorded MAP signal. We obtained a consistent answer in every experiment of each series.
Dr. Franz is correct that the effects of KCl and cold can rapidly dissipate in time and diffuse in space. It is for this reason that we probed the tissue with two microelectrodes at clearly defined distances from the KCl/ATX injection/cooling sites and consistently demonstrated the local distribution of effects of KCl, ATX or cooling at the time the MAP recordings were obtained.
On the question of the local electrogram contamination, please see [4] and below.
It is well known that, in the myocardial syncytium with a limited extracellular space, the extracellular potential has the same time course as the transmembrane potential, but an opposite polarity (note minus sign in this expression for the core-conductor model, Eq. (35) in [5]):
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Depolarization of the cellular membrane during the action potential is due to the movement of cations into the cell. Their departure from the limited extracellular space creates a negative charge and an inverted image of the transmembrane action potential. In order to obtain a positive (monophasic) action potential signal, the extracellular recording must be inverted. That is precisely what is done in all MAP recordings: the electrode at the inactive site is connected to the positive input of an amplifier while the electrode at the active site is connected to the negative input, thus reversing the polarity of the recorded signal. Thus, contrary to Dr. Franz's claim, consideration of the polarity of the recorded MAP signal actually confirms our interpretation of the basis for the MAP.
Experiments shown in Fig. 6 were designed to probe whether the tissue at the border of the area depolarized by mechanical pressure or KCl injection contributes to the MAP signal recorded by either contact or KCl-referenced MAP technique. ATX-II injection close to the inactivated site had no effect on the recorded MAP signal. In contrast, when ATX-II was injected near the other electrode, the expected prolongation of the MAP signal was readily observed.
There are many methods to compute the monophasic action potential signal. The solid angle approach is useful when recording is made outside the volume containing the active sources. If tissue can be considered generally homogeneous in terms of resistivity (no macroscopic internal discontinuities), then we can combine Eqs. (35) and (19) in [5] to estimate the potential at any external point as an integral over the boundary surface S (compare with Eq. (20) in [5]):
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where Vm is the transmembrane potential of the surface cells, ro and ri are corresponding external and internal resistivities, and d
is the solid angle subtended by a surface element. Each electrode–at the catheter tip and the proximal one–"sees" the same voltage distribution Vm along this boundary surface. However, the electrical potential at these two sites will be different due to the different solid angles. According to the definition of the solid angle:
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where dS is the area of the surface element, r is the distance from the recording site to this element measured along the boundary surface, h is the fixed vertical distance between an electrode and this surface (few microns vs. 5 mm). Thus, the contribution of the distal activity decreases as 1/r3 for distances much larger than h. The tip electrode located just above the surface gets a contribution from an area that is almost completely depolarized by the mechanical pressure of the same electrode so that potential at the tip electrode is essentially constant in time. The second electrode, located 5 mm above the surface, will be sensitive to a much wider area that includes normal active tissue around inactivated area and its potential will vary with the transmembrane voltage Vm. The 5 mm distance above the surface is still much smaller than the size of our preparation or the ventricular wall so that total solid angle will be not much different from 2
, i.e. no noticeable attenuation of the potential with distance will occur. Therefore, the MAP signal–the difference of potentials between the two electrodes–will vary in time together with Vm supplied by the proximal electrode. This brief analysis shows that solid angle approach is consistent with our interpretation of the MAP recording.
Experiments recently reported by Franz and coworker [6] were based on the assumption that a "common" electrode connected to the ground has some special properties compared with other electrodes. Actually, both "common" (C) and reference (R) electrodes are in the bath solution and are equivalently sensitive to the activity of the normal myocardial tissue with the only difference being that the R electrode is closer to the surface. However, due to the high conductivity of saline, resistances between either the R electrode or C electrode and the myocardial surface are rather similar. Therefore, both electrodes experience almost the same time-dependent changes of potential, leading to electrogram-like recording between them. On the other hand, the tip electrode (T) is firmly positioned in the center of the depolarized area and potential at this site practically does not change in time. Therefore, the voltage difference between this and either the R electrode or C electrode will be almost identical and reflect average transmembrane potential of surface cardiomyocytes. Since extracellular potential has opposite polarity compared to the transmembrane voltage, both electrodes (R and C) must be connected to the negative inputs, while the tip electrode must be connected to the positive inputs so that the polarity of the recorded signal is reversed.
Dr. Franz considers local electrograms or cardiographic signals as an intrinsic property of the active myocardium similar to transmembrane ionic currents or intercellular currents responsible for impulse propagation. We take strong exception to this view. Electrograms or electrocardiograms (like the MAP) are time-dependent signals that are recorded from the active heart using a specific electrode configuration. When two electrodes are gently placed on the heart surface, the recorded signal is called a bipolar electrogram. When mechanical pressure is applied on one of the electrodes to permanently depolarize tissue beneath it, the bipolar electrogram becomes an MAP signal. The MAP does not co-exist with the electrogram. Otherwise, we are obliged to assume that the MAP signal is also hidden somewhere in the myocardium (as electrogram) and mechanical pressure reveals this signal and adds it on to the ever-present electrogram.
We agree with Dr. Franz that our discussion is more than one of semantics, as also pointed out by the insightful editorial comment of Dr. Alan Kadish[7]. The literal interpretation of the contact monophasic action potential recording as a purely local response recorded at the tip of the contact electrode is inaccurate and misleading. We respect his opinion, but remain unconvinced by Dr. Franz's arguments; we stand by our data and conclusions.
Vladislav V. Nesterenko
Masahiko Kondo
Charles Antzelevitch
Masonic Medical Research Laboratory
2150 Bleecker Street
Utica, NY 13413
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- Kondo M., Nesterenko V., Antzelevitch C. Cellular basis for the monophasic action potential. which electrode is the recording electrode? Cardiovasc. Res. (2004) 63:635–644.
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- Dower G.E., Ziegler W.G., Geddes M.A., Osborn J.A. Depolarizing-electrode monophasic curves and myocardial infarction ST shift. Am. J. Physiol. (1962) 202:35–40.
[Abstract/Free Full Text] - Nesterenko V.V., Weissenburger J., Antzelevitch C. Cellular basis and method for recording the monophasic action potential. J. Cardiovasc. Electrophysiol. (2000) 11(8):946–951.[Web of Science][Medline]
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- Knollmann B.C., Sirenko S.G., Henriquez C.S., Franz M.R. Origin of the monophasic action potential: which electrode? PACE (2003) 26:996.
- Kadish A. What is a monophasic action potential? Cardiovasc. Res. (2004) 63:580–581.
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