Abstract
1. 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 (Q10 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 Cl- with isethionate, indicating that the voltage change produced by the Na+ current was not modified by passive Cl- 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 Ca2+ and restored by addition of Mg2+. 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.
Full text
PDF![651](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/2caaa6d2b2aa/brjpharm00488-0067.png)
![652](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/139cb8d1d65e/brjpharm00488-0068.png)
![653](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/c679f99e158d/brjpharm00488-0069.png)
![654](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/a4b042d28276/brjpharm00488-0070.png)
![655](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/45af8239b9a6/brjpharm00488-0071.png)
![656](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/9ab1e327070f/brjpharm00488-0072.png)
![657](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/e17c04065d91/brjpharm00488-0073.png)
![658](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/1a739f462010/brjpharm00488-0074.png)
![659](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/b74927cb3906/brjpharm00488-0075.png)
![660](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/125dcdc94cbc/brjpharm00488-0076.png)
![661](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/6a89bf3169a7/brjpharm00488-0077.png)
![662](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/8e5d14767fde/brjpharm00488-0078.png)
![663](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/036d9b6f02db/brjpharm00488-0079.png)
![664](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/d4d0dfb599d1/brjpharm00488-0080.png)
![665](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/713d1adac205/brjpharm00488-0081.png)
![666](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/3bed66149870/brjpharm00488-0082.png)
![667](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/cca5244c0b21/brjpharm00488-0083.png)
![668](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/f29dcdbc9525/brjpharm00488-0084.png)
![669](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/f9ebb8e95b17/brjpharm00488-0085.png)
![670](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/a4560aa7bc03/brjpharm00488-0086.png)
![671](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7e9/1665991/03788d151068/brjpharm00488-0087.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ALDRIDGE W. N. Adenosine triphosphatase in the microsomal fraction from rat brain. Biochem J. 1962 Jun;83:527–533. doi: 10.1042/bj0830527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ARMETT C. J., RITCHIE J. M. The action of acetylcholine and some related substances on conduction in mammalian non-myelinated nerve fibres. J Physiol. 1961 Feb;155:372–384. doi: 10.1113/jphysiol.1961.sp006634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Akera T., Larsen F. S., Brody T. M. The effect of ouabain on sodium- and potassium-activated adenosine triphosphatase from the hearts of several mammalian species. J Pharmacol Exp Ther. 1969 Nov;170(1):17–26. [PubMed] [Google Scholar]
- Armett C. J., Ritchie J. M. On the permeability of mammalian non-myelinated fibres to sodium and to lithium ions. J Physiol. 1963 Jan;165(1):130–140. doi: 10.1113/jphysiol.1963.sp007047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BURNS B. D., PATON W. D. M. Depolarization of the motor end-plate by decamethonium and acetylcholine. J Physiol. 1951 Sep;115(1):41–73. doi: 10.1113/jphysiol.1951.sp004652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker P. F., Blaustein M. P., Hodgkin A. L., Steinhardt R. A. The influence of calcium on sodium efflux in squid axons. J Physiol. 1969 Feb;200(2):431–458. doi: 10.1113/jphysiol.1969.sp008702. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker P. F., Connelly C. M. Some properties of the external activation site of the sodium pump in crab nerve. J Physiol. 1966 Jul;185(2):270–297. doi: 10.1113/jphysiol.1966.sp007987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baylor D. A., Nicholls J. G. After-effects of nerve impulses on signalling in the central nervous system of the leech. J Physiol. 1969 Aug;203(3):571–589. doi: 10.1113/jphysiol.1969.sp008880. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brinley F. J., Jr, Mullins L. J. Sodium fluxes in internally dialyzed squid axons. J Gen Physiol. 1968 Aug;52(2):181–211. doi: 10.1085/jgp.52.2.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown D. A. Depolarization of normal and preganglionically denervated superior cervical ganglia by stimulant drugs. Br J Pharmacol Chemother. 1966 Mar;26(3):511–520. doi: 10.1111/j.1476-5381.1966.tb01833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown D. A. Effects of hexamethonium and hyoscine on the drug-induced depolarization of isolated superior cervical ganglia. Br J Pharmacol Chemother. 1966 Mar;26(3):521–537. doi: 10.1111/j.1476-5381.1966.tb01834.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown D. A. Electrical responses of cat superior cervical ganglia in vivo to some stimulant drugs and their modification by hexamethonium and hyoscine. Br J Pharmacol Chemother. 1966 Mar;26(3):538–551. doi: 10.1111/j.1476-5381.1966.tb01835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown D. A., Scholfield C. N. Potentials in isolated rat superior cervical ganglia produced by nicotine. Br J Pharmacol. 1970 Nov;40(3):559P–561P. [PMC free article] [PubMed] [Google Scholar]
- FRANKENHAEUSER B., HODGKIN A. L. The action of calcium on the electrical properties of squid axons. J Physiol. 1957 Jul 11;137(2):218–244. doi: 10.1113/jphysiol.1957.sp005808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GLYNN I. M. The action of cardiac glycosides on sodium and potassium movements in human red cells. J Physiol. 1957 Apr 3;136(1):148–173. doi: 10.1113/jphysiol.1957.sp005749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gebber G. L., Volle R. L. Mechanisms involved in ganglionic blockade induced by tetramethylammonium. J Pharmacol Exp Ther. 1966 Apr;152(1):18–28. [PubMed] [Google Scholar]
- Glynn I. M. Membrane adenosine triphosphatase and cation transport. Br Med Bull. 1968 May;24(2):165–169. doi: 10.1093/oxfordjournals.bmb.a070620. [DOI] [PubMed] [Google Scholar]
- HARRIS E. J., McLENNAN H. Cation exchanges in sympathetic ganglia. J Physiol. 1953 Sep;121(3):629–637. doi: 10.1113/jphysiol.1953.sp004970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODGKIN A. L., KEYNES R. D. Active transport of cations in giant axons from Sepia and Loligo. J Physiol. 1955 Apr 28;128(1):28–60. doi: 10.1113/jphysiol.1955.sp005290. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hancock J. C., Volle R. L. Enhancement by cesium ions of ganglionic hyperpolarization induced by dimethylphenylpiperazinium (DMPP) and repetitive preganglionic stimulation. J Pharmacol Exp Ther. 1969 Oct;169(2):201–210. [PubMed] [Google Scholar]
- JENKINSON D. H., NICHOLLS J. G. Contractures and permeability changes produced by acetylcholine in depolarized denervated muscle. J Physiol. 1961 Nov;159:111–127. doi: 10.1113/jphysiol.1961.sp006796. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaramillo J., Volle R. L. Effects of lithium on ganglionic hyperpolarization and blockade by dimethylphenylipiperazinium. J Pharmacol Exp Ther. 1968 Nov;164(1):166–175. [PubMed] [Google Scholar]
- KERKUT G. A., THOMAS R. C. AN ELECTROGENIC SODIUM PUMP IN SNAIL NERVE CELLS. Comp Biochem Physiol. 1965 Jan;14:167–183. doi: 10.1016/0010-406x(65)90017-4. [DOI] [PubMed] [Google Scholar]
- KEYNES R. D., SWAN R. C. The permeability of frog muscle fibres to lithium ions. J Physiol. 1959 Oct;147:626–638. doi: 10.1113/jphysiol.1959.sp006265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keynes R. D., Ritchie J. M. The movements of labelled ions in mammalian non-myelinated nerve fibres. J Physiol. 1965 Jul;179(2):333–367. doi: 10.1113/jphysiol.1965.sp007666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koketsu K. Cholinergic synaptic potentials and the underlying ionic mechasims. Fed Proc. 1969 Jan-Feb;28(1):101–112. [PubMed] [Google Scholar]
- Kosterlitz H. W., Lees G. M., Wallis D. I. Further evidence for an electrogenic sodium pump in a mammalian sympathetic ganglion. Br J Pharmacol. 1970 Feb;38(2):464P–465P. [PMC free article] [PubMed] [Google Scholar]
- Kosterlitz H. W., Lees G. M., Wallis D. I. Resting and action potentials recorded by the sucrose-gap method in the superior cervical ganglion of the rabbit. J Physiol. 1968 Mar;195(1):39–53. doi: 10.1113/jphysiol.1968.sp008445. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kuno M., Miyahara J. T., Weakly J. N. Post-tetanic hyperpolarization produced by an electrogenic pump in dorsal spinocerebellar tract neurones of the cat. J Physiol. 1970 Nov;210(4):839–855. doi: 10.1113/jphysiol.1970.sp009245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakajima S., Takahashi K. Post-tetanic hyperpolarization and electrogenic Na pump in stretch receptor neurone of crayfish. J Physiol. 1966 Nov;187(1):105–127. doi: 10.1113/jphysiol.1966.sp008078. [DOI] [PMC free article] [PubMed] [Google Scholar]
- PASCOE J. E. The effects of acetylcholine and other drugs on the isolated superior cervical ganglion. J Physiol. 1956 Apr 27;132(1):242–255. doi: 10.1113/jphysiol.1956.sp005519. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pinsker H., Kandel E. R. Synaptic activation of an electrogenic sodium pump. Science. 1969 Feb 28;163(3870):931–935. doi: 10.1126/science.163.3870.931. [DOI] [PubMed] [Google Scholar]
- RITCHIE J. M., STRAUB R. W. The hyperpolarization which follows activity in mammalian non-medullated fibres. J Physiol. 1957 Apr 3;136(1):80–97. doi: 10.1113/jphysiol.1957.sp005744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rang H. P., Ritchie J. M. On the electrogenic sodium pump in mammalian non-myelinated nerve fibres and its activation by various external cations. J Physiol. 1968 May;196(1):183–221. doi: 10.1113/jphysiol.1968.sp008502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SKOU J. C. ENZYMATIC BASIS FOR ACTIVE TRANSPORT OF NA+ AND K+ ACROSS CELL MEMBRANE. Physiol Rev. 1965 Jul;45:596–617. doi: 10.1152/physrev.1965.45.3.596. [DOI] [PubMed] [Google Scholar]
- TAKESHIGE C., PAPPANO A. J., DEGROAT W. C., VOLLE R. L. GANGLIONIC BLOCKADE PRODUCED IN SYMPATHETIC GANGLIA BY CHOLINOMIMETIC DRUGS. J Pharmacol Exp Ther. 1963 Sep;141:333–342. [PubMed] [Google Scholar]
- TAKESHIGE C., VOLLE R. L. A COMPARISON OF THE GANGLION POTENTIALS AND BLOCK PRODUCED BY ACETYLCHOLINE AND TETRAMETHYLAMMONIUM. Br J Pharmacol Chemother. 1964 Aug;23:80–89. doi: 10.1111/j.1476-5381.1964.tb01568.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- TAKEUCHI N. Some properties of conductance changes at the end-plate membrane during the action of acetylcholine. J Physiol. 1963 Jun;167:128–140. doi: 10.1113/jphysiol.1963.sp007136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas R. C. Membrane current and intracellular sodium changes in a snail neurone during extrusion of injected sodium. J Physiol. 1969 Apr;201(2):495–514. doi: 10.1113/jphysiol.1969.sp008769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wespi H. H. Active transport and passive fluxes of K, Na, and Li in mammalian non-myelinated nerve fibres. Pflugers Arch. 1969;306(3):262–280. doi: 10.1007/BF00592437. [DOI] [PubMed] [Google Scholar]
- Woodward J. K., Bianchi C. P., Erulkar S. D. Electrolyte distribution in rabbit superior cervical ganglion. J Neurochem. 1969 Mar;16(3):289–299. doi: 10.1111/j.1471-4159.1969.tb10367.x. [DOI] [PubMed] [Google Scholar]
- den Hertog A., Ritchie J. M. A comparison of the effect of temperature, metabolic inhibitors and of ouabain on the electrogenic componen of the sodium pump in mammalian non-myelinated nerve fibres. J Physiol. 1969 Oct;204(3):523–538. doi: 10.1113/jphysiol.1969.sp008929. [DOI] [PMC free article] [PubMed] [Google Scholar]