Physiol Rev 95: 693– 694, 2015
doi:10.1152/physrev.00006.2015
Letter to the Editor
REPLY TO O’GRADY ET AL.
Kenton M. Sanders, Sean M. Ward, and Sang Don Koh
University of Nevada School of Medicine, Reno, Nevada
This is a reply to a Letter to the Editor (O’Grady G, Angeli T, Du P,
Cheng LK. Concerning the validity of gastrointestinal extracellular
recordings. Physiol Rev 95: 691– 692, 2015. doi:10.1152/
physrev.00005.2015).
stabilization of movements does not seem likely in GI
muscles in vivo because pulsatile flow of blood, respiration, etc. must still occur. Evidence of these movements is
not apparent in the figures provided, so one wonders just
how carefully movement was resolved. We have found
that movements of ⬍50 ␮m generate movement potentials similar to the events typically claimed to be slow
waves. Thus we are doubtful, from their data, that movements in both layers of muscle (under their electrode
arrays) were suppressed.
Early in our communications on this topic, we offered to
collaborate with Dr. O’Grady and to perform tests on several species to resolve whether three extracellular recordings are suitable for recordings of slow waves in GI muscles.
We believe that proper control experiments must include
tests on muscle sheets, in vitro, where slow waves are undisturbed and movements can be stabilized (see suggested
protocols in Ref. 3), but such a collaboration has not taken
place. We once again extend such an invitation for collaboration to Dr. O’Grady and his colleagues to test electrical
recording techniques and parameters they deem ideal on
muscle sheets in which motion is stabilized unequivocally
and electrical slow waves persist.
Several reasons make it important to determine unequivocally whether extracellular recording provides valid electrophysiological information. i) Much that we know about
whole organ GI electrophysiology, especially in humans, is
dependent on whether electrical or mechanical behavior is
recorded by this method. For example, classic studies show
that human gastric electrical activity occurs at 3 cycles per
min (cpm) (6), yet two labs have shown higher frequency
slow waves in human gastric muscles when intracellular
microelectrode recording was used (5, 9). ii) Extracellular
recording is performed on human patients in gastroenterology clinics (1, 4, 7). The technique, called electrogastrography, is used to diagnose electrical abnormalities thought to
explain gastric emptying disorders and gastroparesis.
Doesn’t it seem imperative to determine whether electrogastrography is a valid clinical procedure or an artifact of complex abdominal movements? iii) Dr. O’Grady and colleagues perform electrical recordings on human patients
during abdominal surgery (8). iv) Would the risk-to-benefit
ratio for these studies be acceptable if the techniques used to
measure GI electrophysiology were not valid?
The best resolution of this controversy, as communicated to Dr. O’Grady in September of 2010, would be to
perform rigorous control experiments that satisfy all criticism. We took it upon ourselves to perform such control
experiments, and the results left us deeply skeptical about
the validity of extracellular recording in visceral smooth
muscles and the results and interpretations from many
classic studies of GI electrophysiology. Therefore, we
conveyed this concern in our review.
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TO THE EDITOR: In our recent review of interstitial cells in
smooth muscle function (10), we questioned the value of
extracellular recording from visceral smooth muscles without controls for movement, a well known contaminant of
extracellular recordings of biopotentials. In GI muscles,
electrophysiological events (slow waves) are small in amplitude (i.e., ⬍60 mV) and slow to develop (⬍2 V/s) in contrast to the excitable events of heart, skeletal muscle, and
neurons. Slow waves are generated and propagate actively
by a relatively small number of cells (interstitial cells of
Cajal) buried within smooth muscle tissues. These factors
confound the ability to record field potentials, especially
when contractile movements overlap these events in time
(3). Thus, to validate the recording technique and convince
skeptics like ourselves who have performed control experiments on sheets of smooth muscle tissue from four species
in vitro, it seems logical, and frankly a matter of scientific
necessity, to perform controls very carefully before concluding that signals recorded from visceral smooth muscles
with extracellular electrodes are primary recordings of electrophysiological events. Actually, few studies over the decades have performed controls for movement artifacts, and
based on our observations with human, dog, monkey, and
mouse gastric muscles, we questioned whether recordings
in the literature are valid representations of electrophysiological events or artifacts of movement. While we have not
yet published our studies on dog, monkey, and human muscles, we have presented our findings at international meetings attended by Dr. O’Grady and two of his colleagues.
They apparently discount our results and question our ability to record electrical events with surface electrodes. We
have reported our techniques and have shown our methods
and filtering parameters to be suitable for capturing the
kinetics of authentic slow waves in GI muscles (3).
We thought progress was possible when a paper appeared in the Journal of Physiology, in which movement
stabilization was attempted in studies of pig small intestine and stomach (2). However, the controls described
did not muster confidence, and we commented on the
shortcomings in our review. i) Dihydropyridines reduce,
but do not block, contractile movements in many GI
muscles, if one views the tissues with adequate magnification. No information was provided about the efficacy
of these compounds in blocking circular and longitudinal
muscle contractions in the pig. ii) We were not concerned
with the dose of dihydropyridine administered to the pig
but with the concentration effectiveness in blocking contractions of longitudinal and circular muscles. iii) True
DISCLOSURES
4. Chen JD, McCallum RW. Clinical applications of electrogastrography. Am J Gastroenterol 88: 1324 –1336, 1993.
No conflicts of interest, financial or otherwise, are declared
by the author(s).
5. el-Sharkawy TY, Morgan KG, Szurszewski JH. Intracellular electrical activity of canine
and human gastric smooth muscle. J Physiol 279: 291–307, 1978.
6. Hinder RA, Kelly KA. Human gastric pacesetter potential. Site of origin, spread, and response to gastric transection and proximal gastric vagotomy. Am J Surg 133: 29 –33, 1977.
7. Koch KL. Electrogastrography: physiological basis and clinical application in diabetic
gastropathy. Diabetes Technol Therap 3: 51– 62, 2001.
REFERENCES
1. Abell TL, Malagelada JR. Electrogastrography. Current assessment and future perspectives. Digestive Dis Sci 33: 982–992, 1988.
2. Angeli TR, Du P, Paskaranandavadivel N, Janssen PW, Beyder A, Lentle RG, Bissett IP,
Cheng LK, O’Grady G. The bioelectrical basis and validity of gastrointestinal extracellular slow wave recordings. J Physiol 591: 4567– 4579, 2013.
694
9. Rhee PL, Lee JY, Son HJ, Kim JJ, Rhee JC, Kim S, Koh SD, Hwang SJ, Sanders KM, Ward SM.
Analysis of pacemaker activity in the human stomach. J Physiol 589: 6105–6118, 2011.
10. Sanders KM, Ward SM, Koh SD. Interstitial cells of Cajal: regulators of smooth muscle
function. Physiol Rev 94: 859 –907, 2014.
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3. Bayguinov O, Hennig GW, Sanders KM. Movement based artifacts may contaminate
extracellular electrical recordings from GI muscles. Neurogastroenterol Motil 23: 1029 –
1042, e498, 2011.
8. O’Grady G, Angeli TR, Du P, Lahr C, Lammers WJ, Windsor JA, Abell TL, Farrugia G,
Pullan AJ, Cheng LK. Abnormal initiation and conduction of slow-wave activity in
gastroparesis, defined by high-resolution electrical mapping. Gastroenterology 143:
589 –598, e581– e583, 2012.