This Week’s Citation Classic® r~f~IflPfllR. A new method for measuring membrane potentials with external electrodes. Experientia 10:508-9, 1954. [Physiological Institute, University of Berne. Switzerland and Physiological Institute, Saar- University, Homburg, Saarland. Federal Republic of Germanyl This was the first publication of the newly invented After my return to Switzerland, I had difficulties “sucrose gap” method, which allows a short stretch in using the sophisticated methods to determine ofnerve or muscle fibre to be irrigated by an isotonic membrane potentials and decided to try a new way sucrose solution of high specific resistance. The of obtaining a high external resistance. If an ion-free external longitudinal resistance can grow to a multiple isotonic sucrose solution flowed along a bundle of of the core resistance, so that differences between the excitable membranes on or muscle fibres in a gap, ions would be con- either side of the gap can5 be measured at almost their tinuously removed and the resistance would become absolute value. [The SC! indicates that this paper has much higher than in ordinary paraffin oil or even air been cited in over 290 publications since 1955.1 gaps. Such a sucrose gap (as I named it), when using isotonic KCI.Ringers with a bundle of myelinated nerve fibres, could measure about 90 percent or more of the nodal membrane potential value pub- Robert StkmpfIi lished by Huxley and me. I wrote a short paper and First Institute of Physiology asked Huxley for critical comments. He sent a hand- Medical Faculty of the Saar-University written letter of 12 pages, 7 of them with calcula- 0-6650 Homburg tions to estimatethe errors caused by nonuniformity Federal Republic of Germany of the resistances and by junction potentials. To his surprisethe errors were smaller than expected. His conclusion was: “In the end I quite expect that the March 9, 1988 errorsare trivial and that it is all fuss about nothing. If the errors aren’t bad—say only a few mV—the This short publication ofa method owes its numer- method is extremely useful and convenient.” ous citations to the fact that it contains an absolutely Most people who have u~ilit sii~ihi,~it1iall new idea. During my three autumnal stays of three kinds of excitable tissues of adequate dimensions, months each at the ends of 1947, 1948, and 1949 seem to agree with him. Edith Bulbring, discouraged in Cambridge with and Andrew by intracellular measurements in smooth muscle, had Huxley, I became more aware thatcurrents that flow wanted to abandon electrophysiology until G. Bum- along nerve fibres can best be measured if a high stock brought the sucrose gap method to Oxford. He had it from R.W. Straub, who was my first pupil in resistance gap is produced either by pulling the 2 3 preparation through a hole or through paraffin oil, Homburg to use it in his thesis. ’ This earned me thus reducing the volume ofthe external conducting the compliment of having saved her from giving up. medium. Huxley and I published a method to The theoretical problems contained in Huxley’s letter measure the absolute value of resting and action have been treated by many colleagues.sa One of potentials of a single node of Ranvier by reducing them, John W. Moore, when I visited him, presented the longitudinal current to zero by an electromotive me to the audience as “sugar daddy,” which may force applied to the same external circuit. Such gaps, not have been so complimentary. Among many other however, never have a high enough resistance to more or less successful attempts9 to improve the measure nearly 100 percent of the membrane method is one by C.H.V. Hoyle, where some more potential, which should be possible if the external citations may be found. My conclusion after so many longitudinal resistance exceeds the internal one by years in the era is that there is, particu- more than 10-fold. The surface of the preparation larly in pharmacology, a need for simple methods always remains covered with a film of conducting to measure membrane potentials and thatmy origi- solution and gains ions through the surface nal idea is still useful. An improved version of the membranes. gap (among many others) is cited in reference 9.

I. Huxley A. Personal communication. 25 Apnl 1954. 2. Burnstock G & Straub R W. A method for studying the effects of ions and drugs on resting and action potentials in smooth muscle with external electeodes. J. Physiol.—London 140:156-67. 1958. (Cited 215 dines.) 3. Bdlbring E & Bura~tockG. Membrane potential changes assoctatud with tachyphylaxis and potentiation of the response to stimulating drugs in smooth muscle. Rnr. I. Pttannacol. 15:611-24. 1960. (Cited 125 times.) 4. Pooler J P & Valnozano D P. Reexamination of the double sucrose gap technique for the study of lobster giant . Theory and experiments. Biopisysicai J. 44:261-9, 1983. 5. Lainniel E. A theoretical study on the sucrose gap technique as applied to multiceflular muscle preparations. 1. Saline- sucrose imet’diffusion. Biophysicai 1. 36:533-53, 1981. 6. - A theoretical study on the sucrose gap technique as applied to multicetular muscle preparations. U. Methodical errors in the determination of outward currents. Biopt’tysical 1. 36:555-73, 1981. 7. A theoretical study on the sucrose gap technique as applied to multtceliular muscle preparations. Ill. Methodical errors in the determination of inward currents. Hiophysical 1. 42:159-70, 1983. 8. Moore .1 W. Companson of with microelectzodes and sucrose gap techniques. (Smith I G, Lecar H, Redman S J & Gage P W, mis.) Voltage and parch clamping with microelectrctdes. Bethesda. MD: American Physiological Society, 1985. p. 217-30. 9. Hoyle C H V. A modified single sucrose gap. Junction potentials and electrototuc potentials in gastrointestinal smooth muscles. I. Phannacol. Methods 18:219-26, 1987.

CURRENT CONTENTS® ©l988byISl® LS. V. 31. #34. Aug. 22, 1988 19