Premium
Rate dependency of delayed rectifier currents during the guinea‐pig ventricular action potential
Author(s) -
Rocchetti Marcella,
Besana Alessandra,
Gurrola Georgina B.,
Possani Lourival D.,
Zaza Antonio
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00721.x
Subject(s) - repolarization , time constant , chemistry , ventricular action potential , voltage clamp , cardiology , medicine , diastole , membrane potential , biophysics , electrophysiology , biology , blood pressure , electrical engineering , biochemistry , engineering
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 IKr 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.