![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 55, Issue 5, 812-820, May 1999
Program in Pharmacology and Toxicology (J.V.S., A.J.Y.) and
Departments of
Physiology and Pharmacology (A.J.Y.), University of
Arizona, College of Medicine, Tucson Arizona
Kv1.2 and Kv1.5 are two subtypes of voltage-gated potassium channels
expressed in heart that are thought to contribute to phase 1 (ITO) and phase 3 (IK) components of cardiac
action potential repolarization. Although the effect of
decreased pH in prolonging cardiac action potentials is well
documented, the molecular target of acidification has not previously
been determined. We expressed Kv1.2 and Kv1.5 in Xenopus
oocytes to study the effect of acidic and alkaline extracellular pH on
channel function. Using two-electrode voltage clamp and
cellattached patch clamp, we demonstrate that Kv1.5 channels show
enhanced C-type inactivation at acidic pH that is relevant to
pathophysiological conditions. In contrast, homologous Kv1.2 channels
are resistant to acidic pH. Both channel types are insensitive to
alkaline pH. A histidine residue in the third extracellular loop of
Kv1.5 (H452) accounts for the difference in pH sensitivity between the
Kv1.5 and Kv1.2 channels. Mutation of histidine H452 to a glutamine
residue in Kv1.5 yields a channel that no longer shows enhanced
inactivation with acidification. These data provide insight into
mechanisms subserving known pH effects on cellular signaling functions.
Our results demonstrate that H452 in the third extracellular loop of
Kv1.5 plays a role in C-type inactivation, thus expanding the known
complement of protein regions that contribute to the slow
K+ channel inactivation mechanism.
This article has been cited by other articles:
|
|
 |
|
  A. Cohen, Y. Ben-Abu, S. Hen, and N. Zilberberg A Novel Mechanism for Human K2P2.1 Channel Gating: FACILITATION OF C-TYPE GATING BY PROTONATION OF EXTRACELLULAR HISTIDINE RESIDUES J. Biol. Chem., July 11, 2008; 283(28): 19448 - 19455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Rezazadeh, H. T. Kurata, T. W. Claydon, S. J. Kehl, and D. Fedida An Activation Gating Switch in Kv1.2 Is Localized to a Threonine Residue in the S2-S3 Linker Biophys. J., December 15, 2007; 93(12): 4173 - 4186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Fountain, A. Cheong, J. Li, N. Y. Dondas, F. Zeng, I. C. Wood, and D. J. Beech Kv1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2719 - H2725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Claydon, M. Vaid, S. Rezazadeh, D. C.H. Kwan, S. J. Kehl, and D. Fedida A Direct Demonstration of Closed-State Inactivation of K+ Channels at Low pH J. Gen. Physiol., April 30, 2007; 129(5): 437 - 455. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kiyoshi, D. Yamazaki, S. Ohya, M. Kitsukawa, K. Muraki, S.-y. Saito, Y. Ohizumi, and Y. Imaizumi Molecular and electrophysiological characteristics of K+ conductance sensitive to acidic pH in aortic smooth muscle cells of WKY and SHR Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2723 - H2734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. H. Kwan, D. Fedida, and S. J. Kehl Single Channel Analysis Reveals Different Modes of Kv1.5 Gating Behavior Regulated by Changes of External pH Biophys. J., February 15, 2006; 90(4): 1212 - 1222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Liu, Z. Zhang, and E. R. Liman Extracellular Acid Block and Acid-enhanced Inactivation of the Ca2+-activated Cation Channel TRPM5 Involve Residues in the S3-S4 and S5-S6 Extracellular Domains J. Biol. Chem., May 27, 2005; 280(21): 20691 - 20699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.P. Barfield, C.H. Yeung, and T.G. Cooper The Effects of Putative K+ Channel Blockers on Volume Regulation of Murine Spermatozoa Biol Reprod, May 1, 2005; 72(5): 1275 - 1281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Tammaro, A. L. Smith, B. L. Crowley, and S. V. Smirnov Modulation of the voltage-dependent K+ current by intracellular Mg2+ in rat aortic smooth muscle cells Cardiovasc Res, February 1, 2005; 65(2): 387 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Putnam, J. A. Filosa, and N. A. Ritucci Cellular mechanisms involved in CO2 and acid signaling in chemosensitive neurons Am J Physiol Cell Physiol, December 1, 2004; 287(6): C1493 - C1526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Somodi, Z. Varga, P. Hajdu, J. G. Starkus, D. I. Levy, R. Gaspar, and G. Panyi pH-dependent modulation of Kv1.3 inactivation: role of His399 Am J Physiol Cell Physiol, October 1, 2004; 287(4): C1067 - C1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. H. Kwan, C. Eduljee, L. Lee, S. Zhang, D. Fedida, and S. J. Kehl The External K+ Concentration and Mutations in the Outer Pore Mouth Affect the Inhibition of Kv1.5 Current by Ni2+ Biophys. J., April 1, 2004; 86(4): 2238 - 2250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kelly and J. Church pH modulation of currents that contribute to the medium and slow afterhyperpolarizations in rat CA1 pyramidal neurones J. Physiol., January 15, 2004; 554(2): 449 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Prole, P. A. Lima, and N. V. Marrion Mechanisms Underlying Modulation of Neuronal KCNQ2/KCNQ3 Potassium Channels by Extracellular Protons J. Gen. Physiol., November 24, 2003; 122(6): 775 - 793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zhang, H. T. Kurata, S. J. Kehl, and D. Fedida Rapid Induction of P/C-type Inactivation Is the Mechanism for Acid-induced K+ Current Inhibition J. Gen. Physiol., February 24, 2003; 121(3): 215 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Ebner and G. Chen Spreading Acidification and Depression in the Cerebellar Cortex Neuroscientist, February 1, 2003; 9(1): 37 - 45. [Abstract] [PDF]
|
|
|
|
|
|
J. G. Trapani and S. J. Korn Effect of External pH on Activation of the Kv1.5 Potassium Channel Biophys. J., January 1, 2003; 84(1): 195 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. W. Claydon, M. R. Boyett, A. Sivaprasadarao, and C. H. Orchard Two pore residues mediate acidosis-induced enhancement of C-type inactivation of the Kv1.4 K+ channel Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1114 - C1121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Geiger, D. Becker, B. Lacombe, and R. Hedrich Outer Pore Residues Control the H+ and K+ Sensitivity of the Arabidopsis Potassium Channel AKT3 PLANT CELL, August 1, 2002; 14(8): 1859 - 1868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Komukai, F. Brette, and C. H. Orchard Electrophysiological response of rat atrial myocytes to acidosis Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H715 - H724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cheong, A. M. Dedman, S. Z. Xu, and D. J. Beech KV{alpha}1 channels in murine arterioles: differential cellular expression and regulation of diameter Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1057 - H1065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ishii, K. Nunoki, T. Yamagishi, H. Okada, and N. Taira Differential Sensitivity of Kv1.4, Kv1.2, and Their Tandem Channel to Acidic pH: Involvement of a Histidine Residue in High Sensitivity to Acidic pH J. Pharmacol. Exp. Ther., April 13, 2001; 296(2): 405 - 411. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Austin and S. Wray Interactions Between Ca2+ and H+ and Functional Consequences in Vascular Smooth Muscle Circ. Res., February 18, 2000; 86(3): 355 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Scott and N. S. Allen Changes in Cytosolic pH within Arabidopsis Root Columella Cells Play a Key Role in the Early Signaling Pathway for Root Gravitropism Plant Physiology, December 1, 1999; 121(4): 1291 - 1298. [Abstract] [Full Text]
|
|
|
|
|
|
Z. Qu, Z. Yang, N. Cui, G. Zhu, C. Liu, H. Xu, S. Chanchevalap, W. Shen, J. Wu, Y. Li, et al. Gating of Inward Rectifier K+ Channels by Proton-mediated Interactions of N- and C-terminal Domains J. Biol. Chem., October 6, 2000; 275(41): 31573 - 31580. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
