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Origin of the after‐hyperpolarization that follows removal of depolarizing agents from the isolated superior cervical ganglion of the rat
Author(s) -
BROWN D. A.,
BROWNSTEIN M. J.,
SCHOLFIELD C. N.
Publication year - 1972
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1972.tb07305.x
Subject(s) - hyperpolarization (physics) , depolarization , biophysics , membrane potential , superior cervical ganglion , hexamethonium , ouabain , chemistry , tetrodotoxin , medicine , endocrinology , biochemistry , biology , sodium , stereochemistry , receptor , organic chemistry , nuclear magnetic resonance spectroscopy
Summary1 Potential changes in isolated rat superior cervical ganglia following addition and removal of depolarizing agents were recorded using a moving‐fluid extracellular electrode system. 2 Ganglionic negativity produced by carbachol was followed by a pronounced ganglionic positivity on washing. This after‐positivity was attributed to hyperpolarization of the ganglion cells since it was unaffected by crushing the postganglionic trunk. 3 The after‐hyperpolarization was selectively depressed by (a) cooling (Q 10 2·3), (b) metabolic inhibitors (cyanide, azide, 2,4‐dinitrophenol), (c) reducing [K + ] o or substituting Cs + for K + , (d) ouabain, and (e) substituting Li + for Na + . This suggested a close dependence on active Na + transport. 4 When K + was restored to K + ‐free solution, or the preparation was warmed rapidly, or when metabolic inhibitors were washed away, the hyperpolarization was rapidly regenerated. The effect of restoring K + indicated that the hyperpolarization was generated directly by the Na + pump. 5 The hyperpolarization was not altered by replacing CI − with isethionate, indicating that the voltage change produced by the Na + current was not modified by passive CI − movements. 6 Hexamethonium added to the washout fluid augmented the after‐hyperpolarization, suggesting that there was a high (cationic) leak current due to continued receptor‐activation on washing with normal Krebs solution. 7 The hyperpolarization was reduced by omission of Ca 2+ and restored by addition of Mg 2+ . This was considered to result from changes in passive membrane permeability. 8 The time‐course of post‐carbachol hyperpolarization accorded with a Na + extrusion process whose rate was directly proportional to [Na + ] i with a rate constant of 0·38 ± 0·02 min −1 at 23–27° C. 9 With increasing concentrations of carbachol, the amplitude of the hyperpolarization increased in proportion to the preceding depolarization, but the rate constant of the hyperpolarization was unchanged. 10 The after‐hyperpolarization was reduced in proportion to the depolarization by hexamethonium, but was not affected by atropine, hyoscine or tetrodotoxin. 11 A hyperpolarization also followed depolarization by acetylcholine or by EDTA in Ca 2+ ‐free solution. 12 Nicotine‐depolarization was not followed by a hyperpolarization unless hexamethonium was added to the washout fluid. This was attributed to prolonged receptor‐stimulation by nicotine. 13 It was concluded that the after‐hyperpolarization was due to the electrogenic extrusion of Na + accumulated in the ganglion cells during the preceding depolarization, with no involvement of specific muscarinic receptors. The relationship of this process to post‐tetanic hyperpolarization and to other forms of drug‐induced ganglionic hyperpolarization is discussed.