|
|
|
|
|
|
|
||
The Journal of General Physiology, Vol 101, 603-626, Copyright © 1993 by The Rockefeller University Press
ARTICLES |
DL Campbell, Y Qu, RL Rasmusson and HC Strauss
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Block of the calcium-independent transient outward K+ current, I(to), by 4-aminopyridine (4-AP) was studied in ferret right ventricular myocytes using the whole cell patch clamp technique. 4-AP reduces I(to) through a closed state blocking mechanism displaying "reverse use- dependent" behavior that was inferred from: (a) development of tonic block at hyperpolarized potentials; (b) inhibition of development of tonic block at depolarized potentials; (c) appearance of "crossover phenomena" in which the peak current is delayed in the presence of 4-AP at depolarized potentials; (d) relief of block at depolarized potentials which is concentration dependent and parallels steady-state inactivation for low 4-AP concentrations (V1/2 approximately -10 mV in 0.1 mM 4-AP) and steady-state activation at higher concentrations (V1/2 = +7 mV in 1 mM 4-AP, +15 mV in 10 mM 4-AP); and (e) reassociation of 4- AP at hyperpolarized potentials. No evidence for interaction of 4-AP with either the open or inactivated state of the I(to) channel was obtained from measurements of kinetics of recovery and deactivation in the presence of 0.5-1.0 mM 4-AP. At hyperpolarized potentials (-30 to - 90 mV) 10 mM 4-AP associates slowly (time constants ranging from approximately 800 to 1,300 ms) with the closed states of the channel (apparent Kd approximately 0.2 mM). From -90 to -20 mV the affinity of the I(to) channel for 4-AP appears to be voltage insensitive; however, at depolarized potentials (+20 to +100 mV) 4-AP dissociates with time constants ranging from approximately 350 to 150 ms. Consequently, the properties of 4-AP binding to the I(to) channel undergo a transition in the range of potentials over which channel activation and inactivation occurs (-30 to +20 mV). We propose a closed state model of I(to) channel gating and 4-AP binding kinetics, in which 4-AP binds to three closed states. In this model 4-AP has a progressively lower affinity as the channel approaches the open state, but has no intrinsic voltage dependence of binding.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. R. Ehrlich, C. Hoche, P. Coutu, C. Metz-Weidmann, W. Dittrich, S. H. Hohnloser, S. Nattel, and H. Gogelein Properties of a Time-Dependent Potassium Current in Pig Atrium: Evidence for a Role of Kv1.5 in Repolarization J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 898 - 906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Ahn, S. E. Kim, H.-J. Jang, M.-J. Kim, D.-J. Rhie, S.-H. Yoon, Y.-H. Jo, M.-S. Kim, K.-W. Sung, and S. J. Hahn Interaction of Riluzole with the Closed Inactivated State of Kv4.3 Channels J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 323 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Patel and D. L. Campbell Transient outward potassium current, 'Ito', phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms J. Physiol., November 15, 2005; 569(1): 7 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. V. Pandit, O. Berenfeld, J. M. B. Anumonwo, R. M. Zaritski, J. Kneller, S. Nattel, and J. Jalife Ionic Determinants of Functional Reentry in a 2-D Model of Human Atrial Cells During Simulated Chronic Atrial Fibrillation Biophys. J., June 1, 2005; 88(6): 3806 - 3821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wang, V. E. Bondarenko, Y. Qu, M. J. Morales, R. L. Rasmusson, and H. C. Strauss Activation properties of Kv4.3 channels: time, voltage and [K+]o dependence J. Physiol., June 15, 2004; 557(3): 705 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ishikawa, Y. Nakamura, N. Saitoh, W.-B. Li, S. Iwasaki, and T. Takahashi Distinct Roles of Kv1 and Kv3 Potassium Channels at the Calyx of Held Presynaptic Terminal J. Neurosci., November 12, 2003; 23(32): 10445 - 10453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Jerng and W. F. Gilly Inactivation and Pharmacological Properties of sqKv1A Homotetramers in Xenopus Oocytes Cannot Account for Behavior of the Squid "Delayed Rectifier" K+ Conductance Biophys. J., June 1, 2002; 82(6): 3022 - 3036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grimaldi, M. Atzori, P. Ray, and D. L. Alkon Mobilization of Calcium from Intracellular Stores, Potentiation of Neurotransmitter-Induced Calcium Transients, and Capacitative Calcium Entry by 4-Aminopyridine J. Neurosci., May 1, 2001; 21(9): 3135 - 3143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-R. Li, B. Yang, H. Sun, and C. M. Baumgarten Existence of a transient outward K+ current in guinea pig cardiac myocytes Am J Physiol Heart Circ Physiol, July 1, 2000; 279(1): H130 - H138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Shibata, K. Nakahira, K. Shibasaki, Y. Wakazono, K. Imoto, and K. Ikenaka A-Type K+ Current Mediated by the Kv4 Channel Regulates the Generation of Action Potential in Developing Cerebellar Granule Cells J. Neurosci., June 1, 2000; 20(11): 4145 - 4155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.-N. Tseng Different State Dependencies of 4-Aminopyridine Binding to rKv1.4 and rKv4.2: Role of the Cytoplasmic Halves of the Fifth and Sixth Transmembrane Segments J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 569 - 577. [Abstract] [Full Text]
|
|
|
|
 |
|
 J.-F. Faivre, T. P.G. Calmels, S. Rouanet, J.-L. Javre, B. Cheval, and A. Bril Characterisation of Kv4.3 in HEK293 cells: comparison with the rat ventricular transient outward potassium current Cardiovasc Res, January 1, 1999; 41(1): 188 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, B. Zhu, J.-A. Yao, and G.-N. Tseng Differential Effects of S6 Mutations on Binding of Quinidine and 4-Aminopyridine to Rat Isoform of Kv1.4: Common Site but Different Factors in Determining Blockers' Binding Affinity J. Pharmacol. Exp. Ther., October 1, 1998; 287(1): 332 - 343. [Abstract] [Full Text]
|
|
|
|
|
|
G.-R. Li, J. Feng, L. Yue, and M. Carrier Transmural heterogeneity of action potentials and Ito1 in myocytes isolated from the human right ventricle Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H369 - H377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-R. Li, H. Sun, and S. Nattel Characterization of a transient outward K+ current with inward rectification in canine ventricular myocytes Am J Physiol Cell Physiol, March 1, 1998; 274(3): C577 - C585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Wang, J. E. Dixon, and D. McKinnon Unexpected and Differential Effects of Cl- Channel Blockers on the Kv4.3 and Kv4.2 K+ Channels : Implications for the Study of the Ito2 Current Circ. Res., November 19, 1997; 81(5): 711 - 718. [Abstract] [Full Text]
|
|
|
|
|
|
S. W. Yeola and D. J. Snyders Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current Cardiovasc Res, March 1, 1997; 33(3): 540 - 547. [Abstract] [PDF]
|
|
|
|
|
|
G. A. Gintant Two Components of Delayed Rectifier Current in Canine Atrium and Ventricle : Does IKs Play a Role in the Reverse Rate Dependence of ClassIII Agents? Circ. Res., January 1, 1996; 78(1): 26 - 37. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Nabauer, D. J. Beuckelmann, P. Uberfuhr, and G. Steinbeck Regional Differences in Current Density and Rate-Dependent Properties of the Transient Outward Current in Subepicardial and Subendocardial Myocytes of Human Left Ventricle Circulation, January 1, 1996; 93(1): 168 - 177. [Abstract] [Full Text]
|
|
|
|
