Abstract
Voltage-dependent sodium channels have a decisive role in the generation of action potentials (AP) in many types of cells. In addition to the fast inactivating Na-current, associated with AP generation, the Na-channel can give rise to a noninactivating or persistent Na-current. The latter current generally comprises up to 5% of the transient current having important physiological consequences. It was established that persistent Na-currents have functional significance in setting the membrane potential in a subthreshold range regulating by this way dendritic depolarisations, repetitive firing and enhancing synaptic transmission. Voltage dependent sodium channel genes have been identified in a variety of invertebrates, as well as mammalian and nonmammalian vertebrates. It has been established that the biophysical properties, pharmacology and gene organization of invertebrate sodium channels are largely similar to the vertebrate ones, supporting the view that the ancestral sodium channel was established before the evolutionary separation of the invertebrates from the vertebrates. Although different isoforms of voltage sensitive Na-channels have now been identified the mechanism for persistent current remains controversial. An important yet unanswered question is whether persistent and fast inactivating Na-currents arise from different sets of sodium channels or whether the persistent Na-current results from different gating of the same channel type. The aim of the present review is to discuss the origin and the function of the persistent current, focusing on data derived from an invertebrate animal.
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Abbreviations
- AP:
-
action potential
- INaP:
-
persistent sodium current
- INaT:
-
fast inactivating sodium current
- AA:
-
amino acid
- DRG:
-
dorsal root ganglion
- TTX:
-
tetrodotoxin
- VDNC:
-
voltage-dependent Nachannel
References
Agrawal, N., Hamam, B. N., Magistretti, J., Alonso, A., Ragsdale, D. S. (2001) Persistent sodium channel activity mediates subthreshold membrane potential oscillations and low-threshold spikes in rat entorhinal cortex layer V neurons. Neuroscienc. 102, 53–64.
Akaike, H. (1974) A new look at the statistical model identification. IEEE Trans. Automatic Contro. 19, 716–723.
Alzheimer, C., Schwindt, P. C., Crill, W. E. (1993) Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex. J. Neurosci. 13, 660–673.
Anderson, P. A. V. (1987) Properties and pharmacology of a TTX-insensitive Na+ current in neurons of the jellyfish Cyanea-Capillata. J. Exp. Biol. 133, 231–248.
Angstadt, J. D. (1999) Persistent inward currents in cultured Retzius cells of the medicinal leech. J. Comp. Physiol. [A]. 184, 49–61.
Armstrong, C. M., Bezanilla, F., Rojas, E. (1973) Destruction of sodium conductance inactivation in squid axons perfused with pronase. J. Gen. Physiol. 62, 375–391.
Brown, A. M., Schwindt, P. C., Crill, W. E. (1994) Different voltage dependence of transient and persistent Na+ currents is compatible with modal-gating hypothesis for sodium channels. J. Neurophysiol. 71, 2562–2565.
Butera, R. J., Jr., Rinzel, J., Smith, J. C. (1999) Models of respiratory rhythm generation in the pre- Botzinger complex. I. Bursting pacemaker neurons. J. Neurophysiol. 82, 382–397.
Caffrey, J. M., Eng, D. L., Black, J. A., Waxman, S. G., Kocsis, J. D. (1992) Three types of sodium channels in adult rat dorsal root ganglion neurons. Brain Res. 592, 283–297.
Chandler, W. K., Meves, H. (1970) Evidence for two types of sodium conductance in axons perfused with sodium fluoride solution. J. Physiol. 211, 653–678.
Chen, N., Lucero, M. T. (1999) Transient and persistent tetrodotoxin-sensitive sodium currents in squid olfactory receptor neurons. J. Comp. Physiol. . 184, 63–72.
Clay, J. R. (2003) On the persistent sodium current in squid giant axons. J. Neurophysiol. 89, 640–644.
Colmers, W. F., Lewis, D. V., Wilson, W. A. (1982) Cs+ loading reveals Na+-dependent persistent inward current and negative slope resistance region in Aplysia giant neurons. J. Neurophysiol. 48, 1191–1200.
Correa, A. M., Bezanilla, F. (1994) Gating of the squid sodium channel at positive potentials: II. Single channels reveal two open states. Biophys. J. 66, 1864–1878.
Cox, J. J., Reimann, F., Nicholas, A. K., Thornton, G., Roberts, E., Springell, K., Karbani, G., Jafri, H., Mannan, J., Raashid, Y., Al-Gazali, L., Hamamy, H., Valente, E. M., Gorman, S., Williams, R., McHale, D. P., Wood, J. N., Gribble, F. M. Woods, C. G. (2006) An SCN9A channelopathy causes congenital inability to experience pain. Natur. 444, 894–898.
Crill, W. E. (1996) Persistent sodium current in mammalian central neurons. Annu. Rev. Physiol. 58, 349–362.
Cummins, T. R., Howe, J. R., Waxman, S. G. (1998) Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel. J. Neurosci. 18, 9607–9619.
Davis, R. E., Stuart, A. E. (1988) A persistent, TTX-sensitive sodium current in an invertebrate neuron with neurosecretory ultrastructure. J. Neurosci. 8, 3978–3991.
Defaix, A., Lapied, B. (2005) Role of a novel maintained low-voltage-activated inward current permeable to sodium and calcium in pacemaking of insect neurosecretory neurons. Invert. Neurosci. 5, 135–146.
Dib-Hajj, S., Black, J. A., Cummins, T. R., Waxman, S. G. (2002) NaN/Nav1.9: a sodium channel with unique properties. Trends Neurosci. 25, 253–259.
Elinder, F., Arhem, P. (1997) Tail currents in the myelinated axon of Xenopus laevis suggest a twoopen- state Na channel. Biophys. J. 73, 179–185.
Fleidervish, I. A., Gutnick, M. J. (1996) Kinetics of slow inactivation of persistent sodium current in layer V neurons of mouse neocortical slices. J. Neurophysiol. 76, 2125–2130.
French, C. R., Sah, P., Buckett, K. J., Gage, P. W. (1990) A voltage-dependent persistent sodium current in mammalian hippocampal neurons. J. Gen. Physiol. 95, 1139–1157.
Gilly, W. F., Armstrong, C. M. (1984) Threshold channels–a novel type of sodium channel in squid giant axon. Natur. 309, 448–450.
Hammarström, A. K. M., Gage, P. W. (1999) Nitric oxide increases persistent sodium current in rat hippocampal neurons. J. Physiolog. 520, 451–461.
Herzog, R. I., Cummins, T. R., Waxman, S. G. (2001) Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons. J. Neurophysiol. 86, 1351–1364.
Hutcheon, B., Miura, R. M., Puil, E. (1996) Subthreshold membrane resonance in neocortical neurons. J. Neurophysiol. 76, 683–697.
Kallen, R. G., Sheng, Z. H., Yang, J., Chen, L. Q., Rogart, R. B., Barchi, R. L. (1990) Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle. Neuro. 4, 233–242.
Kay, A. R., Sugimori, M., Llinas, R. (1998) Kinetic and stochastic properties of a persistent sodium current in mature guinea pig cerebellar Purkinje cells. J. Neurophysiol. 80, 1167–1179.
Kirsch, G. E., Brown, A. M. (1989) Kinetic properties of single sodium channels in rat heart and rat brain. J. Gen. Physiol. 93, 85–99.
Kiss, T. (2003) Evidence for a persistent Na-conductance in identified command neurones of the snail, Helix pomatia. Brain Res. 989, 16–25.
Kiss, T., Pirger, Z., Kemenes, G. (2008) Food aversive conditioning increases persistent current carried in withdrawal interneurons. Learn. Memory (submitted).
Llinas, R., Sugimori, M. (1980) Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. J. Physiol. 305, 171–195.
Magistretti, J., Alonso, A. (1999) Biophysical properties and slow voltage-dependent inactivation of a sustained sodium current in entorhinal cortex layer-II principal neurons: a whole-cell and singlechannel study. J. Gen. Physiol. 114, 491–509.
Magistretti, J., Ragsdale, D. S., Alonso, A. (1999) High conductance sustained single-channel activity responsible for the low-threshold persistent Na(+) current in entorhinal cortex neurons. J. Neurosci. 19, 7334–7341.
Maurice, N., Tkatch, T., Meisner, M., Sprunger, L. K., Surmeier, D. J. (2001) D1/D5 dopamine receptor activation differentially modulates rapidly inactivating and presistent sodium currents in prefrontal cortex pyramid. J. Neurosci. 21, 2268–2277.
Mittmann, T., Alzheimer, C. (1998) Muscarinic inhibition of persistent Na+ current in rat neocortical pyramidal neurons. J. Neurophysiol. 79, 1579–1582.
Nagy, K., Kiss, T., Hof, D. (1983) Single Na channels in mouse neuroblastoma cell membrane. Indications for two open states. Pflugers Arch. 399, 302–308.
Nikitin, E. S., Kiss, T., Staras, K., O’Shea, M., Benjamin, P. R., Kemenes, G. (2006) Persistent sodium current is a target for cAMP-induced neuronal plasticity in a state-setting modulatory interneuron. J. Neurophysiol. 95, 453–463.
Nikitin, E. S., Vavoulis, D. V., Feng, J., O’Shea, M., Benjamin, P. R., Kemenes, G. (2008) Persistent sodium current is a non-synaptic substrate for memory (submitted).
Ochs, G., Bromm, B., Schwarz, J. R. (1981) A three-state model for inactivation of sodium permeability. Biochim. Biophys. Act. 645, 243–252.
Ogata, N., Ohishi, Y. (2002) Molecular diversity of structure and function of the voltage-gated Na+ channels. Jpn. J. Pharmacol. 88, 365–377.
Opdyke, C. A., Calabrese, R. L. (1994) A persistent sodium current contributes to oscillatory activity in heart interneurons of the medicinal leech. J. Comp. Physiol. [A]. 175, 781–789.
Patlak, J. B., Ortiz, M. (1985) Slow currents through single sodium channels of the adult rat heart. J. Gen. Physiol. 86, 89–104.
Patlak, J. B., Ortiz, M. (1986) Two modes of gating during late Na+ channel currents in frog sartorius muscle. J. Gen. Physiol. 87, 305–326.
Plummer, N. W., Meisler, M. H. (1999) Evolution and diversity of mammalian sodium channel genes. Genomic. 57, 323–331.
Raman, I. M., Bean, B. P. (1997) Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons. J. Neurosci. 17, 4517–4526.
Raman, I. M., Bean, B. P. (1999) Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. J. Neurosci. 19, 1663–1674.
Raman, I. M., Bean, B. P. (2001) Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms. Biophys. J. 80, 729–737.
Renganathan, M., Dib-Hajj, S., Waxman, S. G. (2002) Na(v)1.5 underlies the ‘third TTX-R sodium current’ in rat small DRG neurons. Brain Res. Mol. Brain Res. 106, 70–82.
Roy, M. L., Narahashi, T. (1992) Differential properties of tetradotoxin-sensitive and tetrodotoxinresistant sodium channels in rat dorsal root ganglion neurons. J. Neurosci. 12, 2104–2111.
Rudy, B. (1978) Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance. J. Physiol. 283, 1–21.
Saint, D. A., Ju, Y. K., Gage, P. W. (1992) A persistent sodium current in rat ventricular myocytes. J. Physiol. 453, 219–231.
Salgado, V. L., Yeh, J. Z., Narahashi, T. (1985) Voltage-dependent removal of sodium inactivation by N-bromoacetamide and pronase. Biophys. J. 47, 567–571.
Stimers, J. R., Byerly, L. (1982) Slowing of sodium current inactivation by ruthenium red in snail neurons. J. Gen. Physiol. 80, 485–497.
Taddese, A., Bean, B. P. (2002) Subthreshold sodium current from rapidly inactivating sodium channels drives spontaneous firing of tuberomammillary neurons. Neuro. 33, 587–600.
The, Y. K., Fernandes, J., Popa, M. O., Alekov, A. K., Timmer, J., Lerche, H. (2006) Modeling of single noninactivating Na+ channels: evidence for two open and several fast inactivated states. Biophys. J. 90, 3511–3522.
Trimmer, J. S., Cooperman, S. S., Tomiko, S. A., Zhou, J. Y., Crean, S. M., Boyle, M. B., Kallen, R. G., Sheng, Z. H., Barchi, R. L., Sigworth, F. J. et al. (1989) Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuro. 3, 33–49.
Turrigiano, G., LeMasson, G., Marder, E. (1995) Selective regulation of current densities underlies spontaneous changes in the activity of cultured neurons. J. Neurosci. 15, 3640–3652.
Ulbricht, W. (2005) Sodium channel inactivation: molecular determinants and modulation. Physiol. Rev. 85, 1271–1301.
Waxman, S. G., Hains, B. C. (2006) Fire and phantoms after spinal cord injury: Na+ channels and central pain. Trends Neurosci. 29, 207–215.
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Kiss, T. Persistent Na-Channels: Origin and Function. BIOLOGIA FUTURA 59 (Suppl 2), 1–12 (2008). https://doi.org/10.1556/ABiol.59.2008.Suppl.1
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DOI: https://doi.org/10.1556/ABiol.59.2008.Suppl.1