HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rocchetti, M. Articles by Zaza, A. Search for Related Content PubMed PubMed Citation Articles by Rocchetti, M. Articles by Zaza, A.

Rate dependency of delayed rectifier currents during the guinea-pig ventricular action potential

Marcella Rocchetti, Alessandra Besana, Georgina B. Gurrola *, Lourival D. Possani * and Antonio Zaza

1. The action potential clamp technique was exploited to evaluate the rate dependency of delayed rectifier currents (I_Kr and I_Ks) during physiological electrical activity. I_Kr and I_Ks were measured in guinea-pig ventricular myocytes at pacing cycle lengths (CL) of 1000 and 250 ms.
2. A shorter CL, with the attendant changes in action potential shape, was associated with earlier activation and increased magnitude of both I_Kr and I_Ks. Nonetheless, the relative contributions of I_Kr and I_Ks to total transmembrane current were independent of CL.
3. Shortening of diastolic interval only (constant action potential shape) enhanced I_Ks, but not I_Kr.
4. I_Kr was increased by a change in the action potential shape only (constant diastolic interval).
5. In ramp clamp experiments, I_Kr amplitude was directly proportional to repolarization rate at values within the low physiological range (< 1.0 V s^-1); at higher repolarization rates proportionality became shallower and finally reversed.
6. When action potential duration (APD) was modulated by constant current injection (I-clamp), repolarization rates > 1.0 V s^-1 were associated with a reduced effect of I_Kr block on APD. The effect of changes in repolarization rate was independent of CL and occurred in the presence of I_Ks blockade.
7. In spite of its complexity, the behaviour of I_Kr was accurately predicted by a numerical model based entirely on known kinetic properties of the current.
8. Both I_Kr and I_Ks may be increased at fast heart rates, but this may occur through completely different mechanisms. The mechanisms identified are such as to contribute to abnormal rate dependency of repolarization in prolonged repolarization syndromes.

This article has been cited by other articles:

				Y. RUDY Molecular Basis of Cardiac Action Potential Repolarization Ann. N.Y. Acad. Sci., March 1, 2008; 1123(1): 113 - 118. [Abstract] [Full Text] [PDF]

				Y. Rudy Modelling the molecular basis of cardiac repolarization Europace, November 1, 2007; 9(suppl_6): vi17 - vi19. [Abstract] [Full Text] [PDF]

				M. Rocchetti, V. Freli, V. Perego, C. Altomare, G. Mostacciuolo, and A. Zaza Rate dependency of {beta}-adrenergic modulation of repolarizing currents in the guinea-pig ventricle J. Physiol., July 1, 2006; 574(1): 183 - 193. [Abstract] [Full Text] [PDF]

				T. Jespersen, M. Grunnet, and S.-P. Olesen The KCNQ1 Potassium Channel: From Gene to Physiological Function Physiology, December 1, 2005; 20(6): 408 - 416. [Abstract] [Full Text] [PDF]

				J. Silva and Y. Rudy Subunit Interaction Determines IKs Participation in Cardiac Repolarization and Repolarization Reserve Circulation, September 6, 2005; 112(10): 1384 - 1391. [Abstract] [Full Text] [PDF]

				C. Terrenoire, C. E. Clancy, J. W. Cormier, K. J. Sampson, and R. S. Kass Autonomic Control of Cardiac Action Potentials: Role of Potassium Channel Kinetics in Response to Sympathetic Stimulation Circ. Res., March 18, 2005; 96(5): e25 - e34. [Abstract] [Full Text] [PDF]

				F. Hua and R. F. Gilmour Jr Contribution of IKr to Rate-Dependent Action Potential Dynamics in Canine Endocardium Circ. Res., April 2, 2004; 94(6): 810 - 819. [Abstract] [Full Text] [PDF]

				T. Banyasz, L. Fulop, J. Magyar, N. Szentandrassy, A. Varro, and P. P. Nanasi Endocardial versus epicardial differences in L-type calcium current in canine ventricular myocytes studied by action potential voltage clamp Cardiovasc Res, April 1, 2003; 58(1): 66 - 75. [Abstract] [Full Text] [PDF]