|
|
|
|
|
|
|
||
Article |
The Role of Weak Blocking Molecules
Outward currents through the inward rectifier K+ channel contribute to repolarization of the cardiac action potential. The properties of the IRK1 channel expressed in murine fibroblast (L) cells closely resemble those of the native cardiac inward rectifier. In this study, we added Mg2+ (0.44–1.1 mM) or putrescine (
0.4 mM) to the intracellular milieu where endogenous polyamines remained, and then examined outward IRK1 currents using the whole-cell patch-clamp method at 5.4 mM external K+. Without internal Mg2+, small outward currents flowed only at potentials between –80 (the reversal potential) and –40 mV during voltage steps applied from –110 mV. The strong inward rectification was mainly caused by the closed state of the activation gating, which was recently reinterpreted as the endogenous-spermine blocked state. With internal Mg2+, small outward currents flowed over a wider range of potentials during the voltage steps. The outward currents at potentials between –40 and 0 mV were concurrent with the contribution of Mg2+ to blocking channels at these potentials, judging from instantaneous inward currents in the following hyperpolarization. Furthermore, when the membrane was repolarized to –50 mV after short depolarizing steps (>0 mV), a transient increase appeared in outward currents at –50 mV. Since the peak amplitude depended on the fraction of Mg2+-blocked channels in the preceding depolarization, the transient increase was attributed to the relief of Mg2+ block, followed by a re-block of channels by spermine. Shift in the holding potential (–110 to –80 mV), or prolongation of depolarization, increased the number of spermine-blocked channels and decreased that of Mg2+-blocked channels in depolarization, which in turn decreased outward currents in the subsequent repolarization. Putrescine caused the same effects as Mg2+. When both spermine (1 µM, an estimated free spermine level during whole-cell recordings) and putrescine (300 µM) were applied to the inside-out patch membrane, the findings in whole-cell IRK1 were reproduced. Our study indicates that blockage of IRK1 by molecules with distinct affinities, spermine and Mg2+ (putrescine), elicits a transient increase in the outward IRK1, which may contribute to repolarization of the cardiac action potential.
Key Words: inward rectification • Mg2+ • spermine • repolarization • putrescine
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  B. K. Panama and A. N. Lopatin Differential polyamine sensitivity in inwardly rectifying Kir2 potassium channels J. Physiol., March 1, 2006; 571(2): 287 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Shin, F. Shen, and J. R. Huguenard Polyamines Modulate AMPA Receptor-Dependent Synaptic Responses in Immature Layer V Pyramidal Neurons J Neurophysiol, May 1, 2005; 93(5): 2634 - 2643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-H. Yan and K. Ishihara Two Kir2.1 channel populations with different sensitivities to Mg2+ and polyamine block: a model for the cardiac strong inward rectifier K+ channel J. Physiol., March 15, 2005; 563(3): 725 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhabyeyev, T. Asai, S. Missan, and T. F. McDonald Transient outward current carried by inwardly rectifying K+ channels in guinea pig ventricular myocytes dialyzed with low-K+ solution Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1396 - C1403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishihara and T. Ehara Two modes of polyamine block regulating the cardiac inward rectifier K+ current IK1 as revealed by a study of the Kir2.1 channel expressed in a human cell line J. Physiol., April 1, 2004; 556(1): 61 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishihara, D.-H. Yan, S. Yamamoto, and T. Ehara Inward rectifier K+ current under physiological cytoplasmic conditions in guinea-pig cardiac ventricular cells J. Physiol., May 1, 2002; 540(3): 831 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J Zaritsky, J. B Redell, B. L Tempel, and T. L Schwarz The consequences of disrupting cardiac inwardly rectifying K+ current (IK1) as revealed by the targeted deletion of the murine Kir2.1 and Kir2.2 genes J. Physiol., June 15, 2001; 533(3): 697 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Solessio, K. Rapp, I. Perlman, and E. M. Lasater Spermine Mediates Inward Rectification in Potassium Channels of Turtle Retinal Muller Cells J Neurophysiol, April 1, 2001; 85(4): 1357 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Solessio, D. M. Linn, I. Perlman, and E. M. Lasater Characterization With Barium of Potassium Currents in Turtle Retinal Muller Cells J Neurophysiol, January 1, 2000; 83(1): 418 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Takeuchi and M. Ando Voltage-dependent outward K+ current in intermediate cell of stria vascularis of gerbil cochlea Am J Physiol Cell Physiol, July 1, 1999; 277(1): C91 - C99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bailly, M. Mouchoniere, J.-P. Benitah, L. Camilleri, G. Vassort, and P. Lorente Extracellular K+ Dependence of Inward Rectification Kinetics in Human Left Ventricular Cardiomyocytes Circulation, December 15, 1998; 98(24): 2753 - 2759. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishihara and T. Ehara A repolarization-induced transient increase in the outward current of the inward rectifier K+ channel in guinea-pig cardiac myocytes J. Physiol., August 1, 1998; 510(3): 755 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishihara, D.-H. Yan, S. Yamamoto, and T. Ehara Inward rectifier K+ current under physiological cytoplasmic conditions in guinea-pig cardiac ventricular cells J. Physiol., May 1, 2002; 540(3): 831 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
