Abstract
1. The action potential in Myxicola giant axons is abolished if the nerve is stimulated at frequencies higher than about 5 sec-1. At 1 sec-1 the magnitude of the action potential is not maintained upon sequential stimulation but decreases until the response is abolished. 2. The behaviour of the ionic currents underlying the action potential was studied with voltage-clamp techniques to find the origin of such adaptation. These studies showed a frequency-dependent decline of the sodium currents. 3. The decline in the Na currents upon repetitive depolarization is shown to be due to a decrease in the Na conductance and not to change in driving force. 4. An analysis of the effects of conditioning depolarizations on the Na current during a depolarizing test pulse demonstrates that in a single short depolarization (less than 10 msec) 15% of the Na conductance enters an inactivated state from which recovery is very slow. Upon repetitive depolarizations the amount of Na conductance available accumulates in this slowly recovering inactivated state. 5. The data are explained by proposing that every time the membrane is depolarized open channels undergo one of two competing reactions. Open channels enter either the traditional inactivated state described by Hodgkin & Huxley (1952b) from which recovery is fast (a few milliseconds) or an inactivated state from which recovery is very slow (seconds). In Myxicola, only 15% of open channels enter the later inactivated state in a single depolarization. Upon repetitive depolarizations, however, the fraction in this state accumulates if the frequency of pulsing is faster than the rate of recovery. 6. Axons in which the amount of open channels entering the slowly recovering inactivated state is significant, such as in Myxicola, have thus a system capable of storing the previous activity of the axon for periods of seconds or minutes.
Full text
PDF


















Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adelman W. J., Jr, Palti Y. The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei. J Gen Physiol. 1969 Nov;54(5):589–606. doi: 10.1085/jgp.54.5.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Armstrong C. M., Bezanilla F. Charge movement associated with the opening and closing of the activation gates of the Na channels. J Gen Physiol. 1974 May;63(5):533–552. doi: 10.1085/jgp.63.5.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Armstrong C. M., Bezanilla F. Inactivation of the sodium channel. II. Gating current experiments. J Gen Physiol. 1977 Nov;70(5):567–590. doi: 10.1085/jgp.70.5.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker P. F., Meves H., Ridgway E. B. Calcium entry in response to maintained depolarization of squid axons. J Physiol. 1973 Jun;231(3):527–548. doi: 10.1113/jphysiol.1973.sp010247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker P. F., Rink T. J. Catecholamine release from bovine adrenal medulla in response to maintained depolarization. J Physiol. 1975 Dec;253(2):593–620. doi: 10.1113/jphysiol.1975.sp011209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beeler G. W., Jr, Reuter H. Membrane calcium current in ventricular myocardial fibres. J Physiol. 1970 Mar;207(1):191–209. doi: 10.1113/jphysiol.1970.sp009056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Begenisich T. Magnitude and location of surface charges on Myxicola giant axons. J Gen Physiol. 1975 Jul;66(1):47–65. doi: 10.1085/jgp.66.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Binstock L., Goldman L. Current- and voltage-clamped studies on Myxicola giant axons. Effect of tetrodotoxin. J Gen Physiol. 1969 Dec;54(6):730–740. doi: 10.1085/jgp.54.6.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bullock J. O., Schauf C. L. Immobilization of intramembrane charge in Myxicola giant axons. J Physiol. 1979 Jan;286:157–171. doi: 10.1113/jphysiol.1979.sp012611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chandler W. K., Meves H. Slow changes in membrane permeability and long-lasting action potentials in axons perfused with fluoride solutions. J Physiol. 1970 Dec;211(3):707–728. doi: 10.1113/jphysiol.1970.sp009300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Courtney K. R. Mechanism of frequency-dependent inhibition of sodium currents in frog myelinated nerve by the lidocaine derivative GEA. J Pharmacol Exp Ther. 1975 Nov;195(2):225–236. [PubMed] [Google Scholar]
- FRANKENHAEUSER B., HODGKIN A. L. The after-effects of impulses in the giant nerve fibres of Loligo. J Physiol. 1956 Feb 28;131(2):341–376. doi: 10.1113/jphysiol.1956.sp005467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FUORTES M. G., MANTEGAZZINI F. Interpretation of the repetitive firing of nerve cells. J Gen Physiol. 1962 Jul;45:1163–1179. doi: 10.1085/jgp.45.6.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox J. M. Ultra-slow inactivation of the ionic currents through the membrane of myelinated nerve. Biochim Biophys Acta. 1976 Mar 5;426(2):232–244. doi: 10.1016/0005-2736(76)90334-5. [DOI] [PubMed] [Google Scholar]
- Goldman L., Schauf C. L. Quantitative description of sodium and potassium currents and computed action potentials in Myxicola giant axons. J Gen Physiol. 1973 Mar;61(3):361–384. doi: 10.1085/jgp.61.3.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [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]
- HORRIDGE G. A. Analysis of the rapid responses of Nereis and Harmothoë (Annelida). Proc R Soc Lond B Biol Sci. 1959 Mar 17;150(939):245–262. doi: 10.1098/rspb.1959.0019. [DOI] [PubMed] [Google Scholar]
- Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977 Apr;69(4):497–515. doi: 10.1085/jgp.69.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keynes R. D., Rojas E. Kinetics and steady-state properties of the charged system controlling sodium conductance in the squid giant axon. J Physiol. 1974 Jun;239(2):393–434. doi: 10.1113/jphysiol.1974.sp010575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LUETTGAU H. C. THE EFFECT OF METABOLIC INHIBITORS ON THE FATIGUE OF THE ACTION POTENTIAL IN SINGLE MUSCLE FIBRES. J Physiol. 1965 May;178:45–67. doi: 10.1113/jphysiol.1965.sp007613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peganov E. M., Khodorov B. I., Shishkova L. D. Medlennaia natrievaia inaktivatsiia v membrane perekhvata Ranve. Rol' naruzhnogo kaliia. Biull Eksp Biol Med. 1973 Sep;76(9):15–19. [PubMed] [Google Scholar]
- Pelhate M., Pichon Y. Proceedings: Selective inhibition of potassium current in the giant axon of the cockroach. J Physiol. 1974 Oct;242(2):90P–91P. [PubMed] [Google Scholar]
- Rudy B. Proceedings: Slow recovery of the inactivation of sodium conductance in Myxicola giant axons. J Physiol. 1975 Jul;249(1):22P–24P. [PubMed] [Google Scholar]
- Rudy B. Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance. J Physiol. 1978 Oct;283:1–21. doi: 10.1113/jphysiol.1978.sp012485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudy B. Sodium gating currents in Myxicola giant axons. Proc R Soc Lond B Biol Sci. 1976 Jun 30;193(1113):469–475. doi: 10.1098/rspb.1976.0059. [DOI] [PubMed] [Google Scholar]
- Schauf C. L., Bullock J. O., Pencek T. L. Characteristics of sodium tail currents in Myxicola axons. Comparison with membrane asymmetry currents. Biophys J. 1977 Jul;19(1):7–28. doi: 10.1016/S0006-3495(77)85559-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schauf C. L., Pencek T. L., Davis F. A. Slow sodium inactivation in Myxicola axons. Evidence for a second inactive state. Biophys J. 1976 Jul;16(7):771–778. doi: 10.1016/S0006-3495(76)85727-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwarz J. R., Vogel W. Potassium inactivation in single myelinated nerve fibres of Xenopus laevis. Pflugers Arch. 1971;330(1):61–73. doi: 10.1007/BF00588735. [DOI] [PubMed] [Google Scholar]
- Shrager P. Slow sodium inactivation in nerve after exposure to sulhydryl blocking reagents. J Gen Physiol. 1977 Feb;69(2):183–202. doi: 10.1085/jgp.69.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
