Biophysical Journal 61: 941-955 (1992)
© 1992 the Biophysical Society

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ruben, P C Articles by Rayner, M D Search for Related Content PubMed PubMed Citation Articles by Ruben, P C Articles by Rayner, M D

Steady-state availability of sodium channels. Interactions between activation and slow inactivation.

Békésy Laboratory of Neurobiology, Pacific Biomedical Research Center, Honolulu, Hawaii.

ABSTRACT

Changes in holding potential (Vh), affect both gating charge (the Q(Vh) curve) and peak ionic current (the F(Vh) curve) seen at positive test potentials. Careful comparison of the Q(Vh) and F(Vh) distributions indicates that these curves are similar, having two slopes (approximately 2.5e for Vh from -115 to -90 mV and approximately 4e for Vh from -90 to -65 mV) and very negative midpoints (approximately -86 mV). Thus, gating charge movement and channel availability appear closely coupled under fully-equilibrated conditions. The time course by which channels approach equilibration was explored using depolarizing prepulses of increasing duration. The high slope component seen in the F(Vh) and Q(Vh) curves is not evident following short depolarizing prepulses in which the prepulse duration approximately corresponds to the settling time for fast inactivation. Increasing the prepulse duration to 10 ms or longer reveals the high slope, and left-shifts the midpoint to more negative voltages, towards the F(Vh) and Q(Vh) distributions. These results indicate that a separate slow-moving voltage sensor affects the channels at prepulse durations greater than 10 ms. Charge movement and channel availability remain closely coupled as equilibrium is approached using depolarizing pulses of increasing durations. Both measures are 50% complete by 50 ms at a prepulse potential of -70 mV, with proportionately faster onset rates when the prepulse potential is more depolarized. By contrast, charge movement and channel availability dissociate during recovery from prolonged depolarizations. Recovery of gating charge is considerably faster than recovery of sodium ionic current after equilibration at depolarized potentials. Recovery of gating charge at -140 mV, is 65% complete within approximately 100 ms, whereas less than 30% of ionic current has recovered by this time. Thus, charge movement and channel availability appear to be uncoupled during recovery, although both rates remain voltage sensitive. These data suggest that channels remain inactivated due to a separate process operating in parallel with the fast gating charge. We demonstrate that this behavior can be simulated by a model in which the fast charge movement associated with channel activation is electrostatically-coupled to a separate slow voltage sensor responsible for the slow inactivation of channel conductance.

This article has been cited by other articles:

				K. Dougherty, J. A. De Santiago-Castillo, and M. Covarrubias Gating Charge Immobilization in Kv4.2 Channels: The Basis of Closed-State Inactivation J. Gen. Physiol., February 25, 2008; 131(3): 257 - 273. [Abstract] [Full Text] [PDF]

				W. Ouyang, G. Wang, and H. C. Hemmings Jr Isoflurane and Propofol Inhibit Voltage-Gated Sodium Channels in Isolated Rat Neurohypophysial Nerve Terminals Mol. Pharmacol., August 1, 2003; 64(2): 373 - 381. [Abstract] [Full Text] [PDF]

				H. L Tan, C. R Bezzina, J. P.P Smits, A. O Verkerk, and A. A.M Wilde Genetic control of sodium channel function Cardiovasc Res, March 15, 2003; 57(4): 961 - 973. [Abstract] [Full Text] [PDF]

				J. R. Clay On the Persistent Sodium Current in Squid Giant Axons J Neurophysiol, January 1, 2003; 89(1): 640 - 644. [Abstract] [Full Text] [PDF]

				R. F. Rakowski, D. C. Gadsby, and P. De Weer Single Ion Occupancy and Steady-state Gating of Na Channels in Squid Giant Axon J. Gen. Physiol., February 22, 2002; 119(3): 235 - 250. [Abstract] [Full Text] [PDF]

				J.-F. Desaphy, S. Pierno, C. Leoty, A. L. George Jr, A. De Luca, and D. C. Camerino Skeletal muscle disuse induces fibre type-dependent enhancement of Na+ channel expression Brain, June 1, 2001; 124(6): 1100 - 1113. [Abstract] [Full Text] [PDF]

				D. W. Wang, N. Makita, A. Kitabatake, J. R. Balser, and A. L. George Jr Enhanced Na+ Channel Intermediate Inactivation in Brugada Syndrome Circ. Res., October 13, 2000; 87 (8): e37 - e43. [Abstract] [Full Text] [PDF]

				R. L. Ruff Effects of temperature on slow and fast inactivation of rat skeletal muscle Na+ channels Am J Physiol Cell Physiol, November 1, 1999; 277(5): C937 - C947. [Abstract] [Full Text] [PDF]

				S. Taverna, G. Sancini, M. Mantegazza, S. Franceschetti, and G. Avanzini Inhibition of Transient and Persistent Na+ Current Fractions by the New Anticonvulsant Topiramate J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 960 - 968. [Abstract] [Full Text]

				A. Toib, V. Lyakhov, and S. Marom Interaction between Duration of Activity and Time Course of Recovery from Slow Inactivation in Mammalian Brain Na+ Channels J. Neurosci., March 1, 1998; 18(5): 1893 - 1903. [Abstract] [Full Text] [PDF]

				H.-Y. Jung, T. Mickus, and N. Spruston Prolonged Sodium Channel Inactivation Contributes to Dendritic Action Potential Attenuation in Hippocampal Pyramidal Neurons J. Neurosci., September 1, 1997; 17(17): 6639 - 6646. [Abstract] [Full Text] [PDF]