Abstract
1. Rat optic nerves were studied using intra-axonal and whole-nerve recording techniques in a sucrose-gap chamber. Constant-current pulses were applied across the outer compartments of the chamber to achieve a current clamp. 2. The nerves displayed a prominent time-dependent conductance increase elicited by a hyperpolarizing constant-current pulse, as evidenced by a relaxation or 'sag' in membrane potential towards resting potential. The inward current began at about 80 ms and reached a steady level over the next 100-200 ms. Its magnitude progressively increased with increasing levels of hyperpolarization. 3. The inward current elicited by hyperpolarization was reduced, but not abolished, when Na+ was reduced from the normal bath concentration of 151 mM to 0 mM. In Na(+)-free solutions the bath K+ concentration, [K+]o, was varied between 0 and 5 mM; the inward current was greatest when [K+]o was 5 mM and was abolished when [K+]o was zero. 4. The inward current was not abolished by tetrodotoxin (TTX), tetraethylammonium (TEA) or 4-aminopyridine (4-AP) suggesting that conventional voltage-dependent sodium and potassium channels do not underlie the time-dependent conductance increase. Low concentrations of Cs+ completely blocked the inward current, and Ba2+ induced a partial block. External application of divalent cations (Cd2+ and Mg2+) did not block the inward current. These properties are similar to the inwardly rectifying conductance observed in a central nervous system neurone. 5. Stimulus-response curves obtained during the hyperpolarization pulse, before and during the conductance increase, indicate that excitability is increased during the conductance increase. This along with the intra-axonal recordings demonstrates that the origin of the increased conductance is axonal and not glial. 6. It is concluded that central nervous system myelinated fibres in rat optic nerve display a prominent time-dependent conductance increase in response to hyperpolarization that depends on both Na+ and K+ and is blocked by Cs+. This conductance is similar to an inward rectifier described for a variety of neurone types. The increased axonal excitability observed during the conductance increase suggests that its functional role may be to maintain or stabilize axonal excitability during periods of intense action potential activity.
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Selected References
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- Adams P. R., Brown D. A., Constanti A. M-currents and other potassium currents in bullfrog sympathetic neurones. J Physiol. 1982 Sep;330:537–572. doi: 10.1113/jphysiol.1982.sp014357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Adrian R. H. Rectification in muscle membrane. Prog Biophys Mol Biol. 1969;19(2):339–369. [PubMed] [Google Scholar]
- Almers W. Potassium conductance changes in skeletal muscle and the potassium concentration in the transverse tubules. J Physiol. 1972 Aug;225(1):33–56. doi: 10.1113/jphysiol.1972.sp009928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Attwell D., Werblin F. S., Wilson M. The properties of single cones isolated from the tiger salamander retina. J Physiol. 1982 Jul;328:259–283. doi: 10.1113/jphysiol.1982.sp014263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bader C. R., Bertrand D., Schwartz E. A. Voltage-activated and calcium-activated currents studied in solitary rod inner segments from the salamander retina. J Physiol. 1982 Oct;331:253–284. doi: 10.1113/jphysiol.1982.sp014372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker M., Bostock H., Grafe P., Martius P. Function and distribution of three types of rectifying channel in rat spinal root myelinated axons. J Physiol. 1987 Feb;383:45–67. doi: 10.1113/jphysiol.1987.sp016395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrett E. F., Barrett J. N., Crill W. E. Voltage-sensitive outward currents in cat motoneurones. J Physiol. 1980 Jul;304:251–276. doi: 10.1113/jphysiol.1980.sp013323. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrett E. F., Barrett J. N. Intracellular recording from vertebrate myelinated axons: mechanism of the depolarizing afterpotential. J Physiol. 1982 Feb;323:117–144. doi: 10.1113/jphysiol.1982.sp014064. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brew H., Gray P. T., Mobbs P., Attwell D. Endfeet of retinal glial cells have higher densities of ion channels that mediate K+ buffering. Nature. 1986 Dec 4;324(6096):466–468. doi: 10.1038/324466a0. [DOI] [PubMed] [Google Scholar]
- Brown D. A., Adams P. R. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature. 1980 Feb 14;283(5748):673–676. doi: 10.1038/283673a0. [DOI] [PubMed] [Google Scholar]
- Brown H., Difrancesco D. Voltage-clamp investigations of membrane currents underlying pace-maker activity in rabbit sino-atrial node. J Physiol. 1980 Nov;308:331–351. doi: 10.1113/jphysiol.1980.sp013474. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Constanti A., Galvan M. Fast inward-rectifying current accounts for anomalous rectification in olfactory cortex neurones. J Physiol. 1983 Feb;335:153–178. doi: 10.1113/jphysiol.1983.sp014526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crepel F., Penit-Soria J. Inward rectification and low threshold calcium conductance in rat cerebellar Purkinje cells. An in vitro study. J Physiol. 1986 Mar;372:1–23. doi: 10.1113/jphysiol.1986.sp015993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DiFrancesco D. A new interpretation of the pace-maker current in calf Purkinje fibres. J Physiol. 1981 May;314:359–376. doi: 10.1113/jphysiol.1981.sp013713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DiFrancesco D. A study of the ionic nature of the pace-maker current in calf Purkinje fibres. J Physiol. 1981 May;314:377–393. doi: 10.1113/jphysiol.1981.sp013714. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DiFrancesco D., Ojeda C. Properties of the current if in the sino-atrial node of the rabbit compared with those of the current iK, in Purkinje fibres. J Physiol. 1980 Nov;308:353–367. doi: 10.1113/jphysiol.1980.sp013475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fain G. L., Lisman J. E. Membrane conductances of photoreceptors. Prog Biophys Mol Biol. 1981;37(2):91–147. doi: 10.1016/0079-6107(82)90021-9. [DOI] [PubMed] [Google Scholar]
- Fain G. L., Quandt F. N., Bastian B. L., Gerschenfeld H. M. Contribution of a caesium-sensitive conductance increase to the rod photoresponse. Nature. 1978 Mar 30;272(5652):466–469. doi: 10.1038/272467a0. [DOI] [PubMed] [Google Scholar]
- Foster R. E., Connors B. W., Waxman S. G. Rat optic nerve: electrophysiological, pharmacological and anatomical studies during development. Brain Res. 1982 Mar;255(3):371–386. doi: 10.1016/0165-3806(82)90005-0. [DOI] [PubMed] [Google Scholar]
- Gallin E. K. Voltage clamp studies in macrophages from mouse spleen cultures. Science. 1981 Oct 23;214(4519):458–460. doi: 10.1126/science.7291986. [DOI] [PubMed] [Google Scholar]
- Gay L. A., Stanfield P. R. Cs(+) causes a voltage-dependent block of inward K currents in resting skeletal muscle fibres. Nature. 1977 May 12;267(5607):169–170. doi: 10.1038/267169a0. [DOI] [PubMed] [Google Scholar]
- Giles W. R., Shibata E. F. Voltage clamp of bull-frog cardiac pace-maker cells: a quantitative analysis of potassium currents. J Physiol. 1985 Nov;368:265–292. doi: 10.1113/jphysiol.1985.sp015857. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gordon T. R., Kocsis J. D., Waxman S. G. Evidence for the presence of two types of potassium channels in the rat optic nerve. Brain Res. 1988 Apr 26;447(1):1–9. doi: 10.1016/0006-8993(88)90959-6. [DOI] [PubMed] [Google Scholar]
- Hagiwara S., Miyazaki S., Moody W., Patlak J. Blocking effects of barium and hydrogen ions on the potassium current during anomalous rectification in the starfish egg. J Physiol. 1978 Jun;279:167–185. doi: 10.1113/jphysiol.1978.sp012338. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hagiwara S., Miyazaki S., Rosenthal N. P. Potassium current and the effect of cesium on this current during anomalous rectification of the egg cell membrane of a starfish. J Gen Physiol. 1976 Jun;67(6):621–638. doi: 10.1085/jgp.67.6.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hagiwara S., Takahashi K. The anomalous rectification and cation selectivity of the membrane of a starfish egg cell. J Membr Biol. 1974;18(1):61–80. doi: 10.1007/BF01870103. [DOI] [PubMed] [Google Scholar]
- Hestrin S. The interaction of potassium with the activation of anomalous rectification in frog muscle membrane. J Physiol. 1981 Aug;317:497–508. doi: 10.1113/jphysiol.1981.sp013839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hotson J. R., Prince D. A., Schwartzkroin P. A. Anomalous inward rectification in hippocampal neurons. J Neurophysiol. 1979 May;42(3):889–895. doi: 10.1152/jn.1979.42.3.889. [DOI] [PubMed] [Google Scholar]
- Kandel E. R., Tauc L. Anomalous rectification in the metacerebral giant cells and its consequences for synaptic transmission. J Physiol. 1966 Mar;183(2):287–304. doi: 10.1113/jphysiol.1966.sp007867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kocsis J. D., Gordon T. R., Waxman S. G. Mammalian optic nerve fibers display two pharmacologically distinct potassium channels. Brain Res. 1986 Sep 24;383(1-2):357–361. doi: 10.1016/0006-8993(86)90040-5. [DOI] [PubMed] [Google Scholar]
- Kocsis J. D., Waxman S. G. Long-term regenerated nerve fibres retain sensitivity to potassium channel blocking agents. Nature. 1983 Aug 18;304(5927):640–642. doi: 10.1038/304640a0. [DOI] [PubMed] [Google Scholar]
- Lindau M., Fernandez J. M. A patch-clamp study of histamine-secreting cells. J Gen Physiol. 1986 Sep;88(3):349–368. doi: 10.1085/jgp.88.3.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayer M. L., Westbrook G. L. A voltage-clamp analysis of inward (anomalous) rectification in mouse spinal sensory ganglion neurones. J Physiol. 1983 Jul;340:19–45. doi: 10.1113/jphysiol.1983.sp014747. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McKinney L. C., Gallin E. K. Inwardly rectifying whole-cell and single-channel K currents in the murine macrophage cell line J774.1. J Membr Biol. 1988 Jul;103(1):41–53. doi: 10.1007/BF01871931. [DOI] [PubMed] [Google Scholar]
- Nelson P. G., Frank K. Anomalous rectification in cat spinal motoneurons and effect of polarizing currents on excitatory postsynaptic potential. J Neurophysiol. 1967 Sep;30(5):1097–1113. doi: 10.1152/jn.1967.30.5.1097. [DOI] [PubMed] [Google Scholar]
- Purpura D. P., Prelevic S., Santini M. Hyperpolarizing increase in membrane conductance in hippocampal neurons. Brain Res. 1968 Feb;7(2):310–312. doi: 10.1016/0006-8993(68)90109-1. [DOI] [PubMed] [Google Scholar]
- Sakmann B., Trube G. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol. 1984 Feb;347:641–657. doi: 10.1113/jphysiol.1984.sp015088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soliven B., Szuchet S., Arnason B. G., Nelson D. J. Voltage-gated potassium currents in cultured ovine oligodendrocytes. J Neurosci. 1988 Jun;8(6):2131–2141. doi: 10.1523/JNEUROSCI.08-06-02131.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spain W. J., Schwindt P. C., Crill W. E. Anomalous rectification in neurons from cat sensorimotor cortex in vitro. J Neurophysiol. 1987 May;57(5):1555–1576. doi: 10.1152/jn.1987.57.5.1555. [DOI] [PubMed] [Google Scholar]
- Standen N. B., Stanfield P. R. A mechanism for the fall in resting potassium conductance of frog skeletal muscle fibres occurring under extreme hyperpolarization [proceedings]. J Physiol. 1978 Sep;282:18P–19P. [PubMed] [Google Scholar]
- Standen N. B., Stanfield P. R. A potential- and time-dependent blockade of inward rectification in frog skeletal muscle fibres by barium and strontium ions. J Physiol. 1978 Jul;280:169–191. doi: 10.1113/jphysiol.1978.sp012379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Standen N. B., Stanfield P. R. Potassium depletion and sodium block of potassium currents under hyperpolarization in frog sartorius muscle. J Physiol. 1979 Sep;294:497–520. doi: 10.1113/jphysiol.1979.sp012943. [DOI] [PMC free article] [PubMed] [Google Scholar]
