help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vilin, Y. Y.
Right arrow Articles by Ruben, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vilin, Y. Y.
Right arrow Articles by Ruben, P. C.

Biophys J, May 2001, p. 2221-2230, Vol. 80, No. 5

A Single Residue Differentiates between Human Cardiac and Skeletal Muscle Na+ Channel Slow Inactivation

Yuriy Y. Vilin, Esther Fujimoto, and Peter C. Ruben

Department of Biology, Utah State University, Logan, Utah 84322 USA

Slow inactivation determines the availability of voltage-gated sodium channels during prolonged depolarization. Slow inactivation in hNaV1.4 channels occurs with a higher probability than hNaV1.5 sodium channels; however, the precise molecular mechanism for this difference remains unclear. Using the macropatch technique we show that the DII S5-S6 p-region uniquely confers the probability of slow inactivation from parental hNaV1.5 and hNaV1.4 channels into chimerical constructs expressed in Xenopus oocytes. Site-directed mutagenesis was used to test whether a specific region within DII S5-S6 controls the probability of slow inactivation. We found that substituting V754 in hNaV1.4 with isoleucine from the corresponding position (891) in hNaV1.5 produced steady-state slow inactivation statistically indistinguishable from that in wild-type hNaV1.5 channels, whereas other mutations have little or no effect on slow inactivation. This result indicates that residues V754 in hNaV1.4 and I891in hNaV1.5 are unique in determining the probability of slow inactivation characteristic of these isoforms. Exchanging S5-S6 linkers between hNaV1.4 and hNaV1.5 channels had no consistent effect on the voltage-dependent slow time inactivation constants [tau (V)]. This suggests that the molecular structures regulating rates of entry into and exit from the slow inactivated state are different from those controlling the steady-state probability and reside outside the p-regions.

Biophys J, May 2001, p. 2221-2230, Vol. 80, No. 5
© 2001 by the Biophysical Society   0006-3495/01/05/2221/10  $2.00


This article has been cited by other articles:


Home page
 Biophys. JHome page
J. Szendroedi, W. Sandtner, T. Zarrabi, E. Zebedin, K. Hilber, S. C. Dudley Jr., H. A. Fozzard, and H. Todt
Speeding the Recovery from Ultraslow Inactivation of Voltage-Gated Na+ Channels by Metal Ion Binding to the Selectivity Filter: A Foot-on-the-Door?
Biophys. J., December 15, 2007; 93(12): 4209 - 4224.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
A. M. Rush, T. R. Cummins, and S. G. Waxman
Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons
J. Physiol., February 15, 2007; 579(1): 1 - 14.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
W. Xiong, Y. Z. Farukhi, Y. Tian, D. DiSilvestre, R. A. Li, and G. F. Tomaselli
A conserved ring of charge in mammalian Na+ channels: a molecular regulator of the outer pore conformation during slow inactivation
J. Physiol., November 1, 2006; 576(3): 739 - 754.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
G. N. Filatov, M. J. Pinter, and M. M. Rich
Resting Potential-dependent Regulation of the Voltage Sensitivity of Sodium Channel Gating in Rat Skeletal Muscle In Vivo
J. Gen. Physiol., July 25, 2005; 126(2): 161 - 172.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
G. N. Filatov and M. M. Rich
Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy
J. Physiol., September 15, 2004; 559(3): 813 - 820.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
W. Sandtner, J. Szendroedi, T. Zarrabi, E. Zebedin, K. Hilber, I. Glaaser, H. A. Fozzard, S. C. Dudley, and H. Todt
Lidocaine: A Foot in the Door of the Inner Vestibule Prevents Ultra-Slow Inactivation of a Voltage-Gated Sodium Channel
Mol. Pharmacol., September 1, 2004; 66(3): 648 - 657.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
E. Zebedin, W. Sandtner, S. Galler, J. Szendroedi, H. Just, H. Todt, and K. Hilber
Fiber type conversion alters inactivation of voltage-dependent sodium currents in murine C2C12 skeletal muscle cells
Am J Physiol Cell Physiol, August 1, 2004; 287(2): C270 - C280.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
K. Kanai, S. Hirose, H. Oguni, G. Fukuma, Y. Shirasaka, T. Miyajima, K. Wada, H. Iwasa, S. Yasumoto, M. Matsuo, et al.
Effect of localization of missense mutations in SCN1A on epilepsy phenotype severity
Neurology, July 27, 2004; 63(2): 329 - 334.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
R. S. Kass
Sodium Channel Inactivation Goes with the Flow
J. Gen. Physiol., June 28, 2004; 124(1): 7 - 8.
[Full Text] [PDF]

Home page
 J. Physiol.Home page
J. Hering, A. Feltz, and R. C. Lambert
Slow inactivation of the CaV3.1 isotype of T-type calcium channels
J. Physiol., March 1, 2004; 555(2): 331 - 344.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
W. Xiong, R. A. Li, Y. Tian, and G. F. Tomaselli
Molecular Motions of the Outer Ring of Charge of the Sodium Channel: Do They Couple to Slow Inactivation?
J. Gen. Physiol., August 25, 2003; 122(3): 323 - 332.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
A. F. Struyk and S. C. Cannon
Slow Inactivation Does Not Block the Aqueous Accessibility to the Outer Pore of Voltage-gated Na Channels
J. Gen. Physiol., September 30, 2002; 120(4): 509 - 516.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the Biophysical Society.