Abstract
1. The intracellular Na activity (aNai) of quiescent sheep heart Purkinje fibres has been measured using Na+-sensitive glass micro-electrodes. The effects of local anaesthetics (procaine and lidocaine) and tetrodotoxin (TTX) have been investigated.
2. Local anaesthetics reduced the steady-state level of the intracellular Na activity in a dose-dependent manner. The highest concentrations used (10-2 M) reduced the intracellular Na activity by about 25%.
3. TTX decreased the steady-state level of the intracellular Na activity. At a concentration of 10-6 g/ml. (3·13 × 10-6 M), TTX produced a decrease in intracellular Na activity of approximately 10%.
4. The initial rate of rise of the intracellular Na activity upon addition of the cardioactive steroid strophanthidin (10-5 M) was used to estimate the net passive Na influx.
5. Procaine (5 × 10-4 M) caused a 50% reduction of this rate of rise of the intracellular Na activity. The highest concentration of procaine used (10-2 M) decreased the rate of rise by approximately 80%.
6. Procaine (5 × 10-3 M) also reduced the rate of rise of intracellular Na produced by the removal of external K (Ko), and prevented the large depolarization associated with the absence of Ko.
7. TTX also produced a decrease in the rate of rise of the intracellular Na activity that occurs upon addition of strophanthidin. A maximum effect was produced in our experiments at a TTX concentration of 10-6 g/ml. At this concentration the rate of rise of intracellular Na activity was reduced by approximately 40% at a membrane potential of -70 mV.
8. We conclude from our experiments that the effects of local anaesthetics and TTX on the intracellular Na activity are brought about by a reduction of the Na permeability of the cell membrane, and that at the normal resting potential, Na entry through TTX-sensitive channels contributes greatly to the total net Na influx.
Full text
PDF![269](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/e34c2e9f471c/jphysiol00780-0275.png)
![270](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/fc67714608b5/jphysiol00780-0276.png)
![271](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/2fc5ec5b6354/jphysiol00780-0277.png)
![272](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/49a530820899/jphysiol00780-0278.png)
![273](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/0dc95b4c7bb2/jphysiol00780-0279.png)
![274](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/d54ceb37377d/jphysiol00780-0280.png)
![275](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/50adf5e83dc4/jphysiol00780-0281.png)
![276](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/97f4eb6c2420/jphysiol00780-0282.png)
![277](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/0715229c7a09/jphysiol00780-0283.png)
![278](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/9ab3933a575a/jphysiol00780-0284.png)
![279](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/9efce61d21f6/jphysiol00780-0285.png)
![280](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/0896ac30e970/jphysiol00780-0286.png)
![281](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/b55d8a1863cc/jphysiol00780-0287.png)
![282](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fc5/1279354/de9da95a6614/jphysiol00780-0288.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnsdorf M. F., Bigger J. T., Jr Effect of lidocaine hydrochloride on membrane conductance in mammalian cardiac Purkinje fibers. J Clin Invest. 1972 Sep;51(9):2252–2263. doi: 10.1172/JCI107034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baer M., Best P. M., Reuter H. Voltage-dependent action of tetrodotoxin in mammalian cardiac muscle. Nature. 1976 Sep 23;263(5575):344–345. doi: 10.1038/263344a0. [DOI] [PubMed] [Google Scholar]
- Baker P. F., Blaustein M. P., Keynes R. D., Manil J., Shaw T. I., Steinhardt R. A. The ouabain-sensitive fluxes of sodium and potassium in squid giant axons. J Physiol. 1969 Feb;200(2):459–496. doi: 10.1113/jphysiol.1969.sp008703. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bigger J. T., Jr, Mandel W. J. Effect of lidocaine on conduction in canine Purkinje fibers and at the ventricular muscle-Purkinje fiber junction. J Pharmacol Exp Ther. 1970 Apr;172(2):239–254. [PubMed] [Google Scholar]
- Blankenship J. E. Tetrodotoxin: from poison to powerful tool. Perspect Biol Med. 1976 Summer;19(4):509–526. doi: 10.1353/pbm.1976.0071. [DOI] [PubMed] [Google Scholar]
- CARMELIET E. E. Chloride ions and the membrane potential of Purkinje fibres. J Physiol. 1961 Apr;156:375–388. doi: 10.1113/jphysiol.1961.sp006682. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen I. S., Strichartz G. R. On the voltage-dependent action of tetrodotoxin. Biophys J. 1977 Mar;17(3):275–279. doi: 10.1016/S0006-3495(77)85656-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis L. D., Temte J. V. Electrophysiological actions of lidocaine on canine ventricular muscle and Purkinje fibers. Circ Res. 1969 May;24(5):639–655. doi: 10.1161/01.res.24.5.639. [DOI] [PubMed] [Google Scholar]
- Deitmer J. W., Ellis D. Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations. J Physiol. 1978 Apr;277:437–453. doi: 10.1113/jphysiol.1978.sp012283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Deitmer J. W., Ellis D. The intracellular sodium activity of cardiac Purkinje fibres during inhibition and re-activation of the Na-K pump. J Physiol. 1978 Nov;284:241–259. doi: 10.1113/jphysiol.1978.sp012539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dudel J., Peper K., Rüdel R., Trautwein W. The effect of tetrodotoxin on the membrane current in cardiac muscle (Purkinje fibers). Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;295(3):213–226. doi: 10.1007/BF01844101. [DOI] [PubMed] [Google Scholar]
- Eckert R., Lux H. D. A voltage-sensitive persistent calcium conductance in neuronal somata of Helix. J Physiol. 1976 Jan;254(1):129–151. doi: 10.1113/jphysiol.1976.sp011225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ellis D. The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres. J Physiol. 1977 Dec;273(1):211–240. doi: 10.1113/jphysiol.1977.sp012090. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Frieden J. Antiarrhythmic drugs. VII. Lidocaine as an antiarrhythmic agent. Am Heart J. 1965 Nov;70(5):713–715. doi: 10.1016/0002-8703(65)90399-6. [DOI] [PubMed] [Google Scholar]
- Gadsby D. C., Cranefield P. F. Two levels of resting potential in cardiac Purkinje fibers. J Gen Physiol. 1977 Dec;70(6):725–746. doi: 10.1085/jgp.70.6.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gianelly R., von der Groeben J. O., Spivack A. P., Harrison D. C. Effect of lidocaine on ventricular arrhythmias in patients with coronary heart disease. N Engl J Med. 1967 Dec 7;277(23):1215–1219. doi: 10.1056/NEJM196712072772301. [DOI] [PubMed] [Google Scholar]
- Gliklich J. I., Hoffman B. F. Sites of action and active forms of lidocaine and some derivatives on cardiac Purkinje fibers. Circ Res. 1978 Oct;43(4):638–651. doi: 10.1161/01.res.43.4.638. [DOI] [PubMed] [Google Scholar]
- HODGKIN A. L., HUXLEY A. F. The dual effect of membrane potential on sodium conductance in the giant axon of Loligo. J Physiol. 1952 Apr;116(4):497–506. doi: 10.1113/jphysiol.1952.sp004719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hille B. Potassium channels in myelinated nerve. Selective permeability to small cations. J Gen Physiol. 1973 Jun;61(6):669–686. doi: 10.1085/jgp.61.6.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isnberg G. Is potassium conductance of cardiac Purkinje fibres controlled by (Ca2+)? Nature. 1975 Jan 24;253(5489):273–274. doi: 10.1038/253273a0. [DOI] [PubMed] [Google Scholar]
- LIKOFF W. Cardiac arrhythmias complicating surgery. Am J Cardiol. 1959 Apr;3(4):427–429. doi: 10.1016/0002-9149(59)90362-5. [DOI] [PubMed] [Google Scholar]
- Lown B., Fakhro A. M., Hood W. B., Jr, Thorn G. W. The coronary care unit. New perspectives and directions. JAMA. 1967 Jan 16;199(3):188–198. [PubMed] [Google Scholar]
- NARAHASHI T., MOORE J. W., SCOTT W. R. TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS. J Gen Physiol. 1964 May;47:965–974. doi: 10.1085/jgp.47.5.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NOBLE D. A modification of the Hodgkin--Huxley equations applicable to Purkinje fibre action and pace-maker potentials. J Physiol. 1962 Feb;160:317–352. doi: 10.1113/jphysiol.1962.sp006849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ochi R., Hashimoto K. The effect of procaine on the passive electrical properties of guinea-pig ventricular muscle. Pflugers Arch. 1978 Dec 15;378(1):1–7. doi: 10.1007/BF00581951. [DOI] [PubMed] [Google Scholar]
- SHANES A. M., FREYGANG W. H., GRUNDFEST H., AMATNIEK E. Anesthetic and calcium action in the voltage-clamped squid giant axon. J Gen Physiol. 1959 Mar 20;42(4):793–802. doi: 10.1085/jgp.42.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz A., Lindenmayer G. E., Allen J. C. The sodium-potassium adenosine triphosphatase: pharmacological, physiological and biochemical aspects. Pharmacol Rev. 1975 Mar;27(01):3–134. [PubMed] [Google Scholar]
- Strichartz G. Molecular mechanisms of nerve block by local anesthetics. Anesthesiology. 1976 Oct;45(4):421–441. doi: 10.1097/00000542-197610000-00012. [DOI] [PubMed] [Google Scholar]
- TAYLOR R. E. Effect of procaine on electrical properties of squid axon membrane. Am J Physiol. 1959 May;196(5):1071–1078. doi: 10.1152/ajplegacy.1959.196.5.1071. [DOI] [PubMed] [Google Scholar]
- Thomas R. C. New design for sodium-sensitive glass micro-electrode. J Physiol. 1970 Sep;210(2):82P–83P. [PubMed] [Google Scholar]
- WEIDMANN S. Effects of calcium ions and local anesthetics on electrical properties of Purkinje fibres. J Physiol. 1955 Sep 28;129(3):568–582. doi: 10.1113/jphysiol.1955.sp005379. [DOI] [PMC free article] [PubMed] [Google Scholar]