| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
1. The transient outward K+ current (Ito) was studied in enzymatically isolated rat ventricular myocytes using the whole-cell patch clamp technique. 2. At holding potentials between -100 and -60 mV, depolarizing pulses activated outward current which was composed of transient and maintained components. These components differed from each other in their activation voltage range as well as in their kinetics of inactivation. 3. The transient component, in turn, appeared to be composed of rapidly and slowly inactivating components. Subtraction of ICa from the total current, or nifedipine pre-treatment, eliminated the slowly inactivating component of Ito indicating that the time course of inactivation of Ito may be contaminated by ICa. 4. Reduction of the holding potential from -100 mV to less negative holding potentials reduced all components of Ito, such that at holding potentials of -40 mV, very little or no Ito could be measured. 5. Elevation of [Ca2+]o activated Ito at holding potentials of -40 mV, and substitution of external Ca2+ by Sr2+ suppressed Ito, consistent with findings from other preparations and in support of a Ca(2+)-activated component of Ito. 6. Elevations of [Ca2+]o, however, also shifted the steady-state activation and inactivation parameters of the transient K+ current, such that a greater proportion of Ito channels were activated at the less negative holding potentials. 7. The shifts in the activation and inactivation parameters of the transient outward current were not mimicked by equivalent changes in external Mg2+. 8. Modulators of Ca2+ release from the sarcoplasmic reticulum (SR) such as caffeine and ryanodine suppressed Ito regardless of whether the myocytes were dialysed with low or high concentrations of Ca2+ buffers (EGTA or BAPTA, 0.5-14 mM) or whether nifedipine was used to block ICa. 9. 4-Aminopyridine (4-AP) blocked Ito in a dose-dependent manner, completely suppressing it at 10 mM. Similarly, tedisamil, a new K+ channel blocker, completely and reversibly blocked Ito at 5-20 microM concentrations. 10. TTX (10 microM) or removal of external Na+ decreased Ito, consistent with the idea that a component of Ito was Na+ activated. Both interventions, however, also shifted the voltage dependence of the activation and inactivation of Ito to more negative potentials, such that at -100 mV neither intervention had a significant effect on Ito. Alterations in [Na+]i had no effect on Ito.(ABSTRACT TRUNCATED AT 400 WORDS)
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 E. Perrier, R. Perrier, S. Richard, and J.-P. Benitah Ca2+ Controls Functional Expression of the Cardiac K+ Transient Outward Current via the Calcineurin Pathway J. Biol. Chem., September 24, 2004; 279(39): 40634 - 40639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-G. Lai, J. Yang, S.-S. Zhou, J. Zhu, G.-R. Li, and T.-M. Wong Involvement of anion channel(s) in the modulation of the transient outward K+ channel in rat ventricular myocytes Am J Physiol Cell Physiol, July 1, 2004; 287(1): C163 - C170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Huang, D Qin, and N El-Sherif Spatial alterations of Kv channels expression and K+ currents in post-MI remodeled rat heart Cardiovasc Res, November 1, 2001; 52(2): 246 - 254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. DONOHOE, B. M. HENDRY, O. V. WALGAMA, F. BERTASO, D. J. HOPSTER, M. J. SHATTOCK, and A. F. JAMES An Altered Repolarizing Potassium Current in Rat Cardiac Myocytes after Subtotal Nephrectomy J. Am. Soc. Nephrol., September 1, 2000; 11(9): 1589 - 1599. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. T. Hulme and C. H. Orchard Effect of acidosis on transient outward potassium current in isolated rat ventricular myocytes Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H50 - H59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Yong, R. Xu, J. G. McLarnon, A. B. Zolotoy, G. N. Beatch, and M. J. A. Walker RSD1000: A Novel Antiarrhythmic Agent with Increased Potency under Acidic and High-Potassium Conditions J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 236 - 244. [Abstract] [Full Text]
|
|
|
|
|
|
H. Honjo, M. Lei, M. R. Boyett, and I. Kodama Heterogeneity of 4-aminopyridine-sensitive current in rabbit sinoatrial node cells Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1295 - H1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
Z. Xu and G. J. Rozanski K+ current inhibition by amphiphilic fatty acid metabolites in rat ventricular myocytes Am J Physiol Cell Physiol, December 1, 1998; 275(6): C1660 - C1667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Courtemanche, R. J. Ramirez, and S. Nattel Ionic mechanisms underlying human atrial action potential properties: insights from a mathematical model Am J Physiol Heart Circ Physiol, July 1, 1998; 275(1): H301 - H321. [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]
|
|
|
|
 |
|
 P. Bailly, J.-P. Benitah, M. Mouchoniere, G. Vassort, and P. Lorente Regional Alteration of the Transient Outward Current in Human Left Ventricular Septum During Compensated Hypertrophy Circulation, August 19, 1997; 96(4): 1266 - 1274. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Barnes and J. W. Jacklet Ionic Currents of Isolated Retinal Pacemaker Neurons: Projected Daily Phase Differences and Selective Enhancement by a Phase-Shifting Neurotransmitter J Neurophysiol, June 1, 1997; 77(6): 3075 - 3084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Qin, Z.-H. Zhang, E. B. Caref, M. Boutjdir, P. Jain, and N. El-Sherif Cellular and Ionic Basis of Arrhythmias in Postinfarction Remodeled Ventricular Myocardium Circ. Res., September 1, 1996; 79(3): 461 - 473. [Abstract] [Full Text]
|
|
|
|
|
|
C. I. Berul and M. Morad Regulation of Potassium Channels by Nonsedating Antihistamines Circulation, April 15, 1995; 91(8): 2220 - 2225. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
