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Role of the Transient Outward Current in Regulating Mechanical Properties of Canine Ventricular Myocytes
Author(s) -
DONG MIN,
YAN SUJUAN,
CHEN YAMEI,
NIKLEWSKI PAUL J.,
SUN XIAOYIN,
CHENAULT KATHRYN,
WANG HONGSHENG
Publication year - 2010
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2009.01708.x
Subject(s) - contractility , myocyte , repolarization , medicine , cardiac transient outward potassium current , endocardium , cardiology , heart failure , endoplasmic reticulum , endocrinology , patch clamp , electrophysiology , microbiology and biotechnology , biology
I to and Myocyte Contractility. Introduction:The transient outward current (I to ) is a major repolarizing current in the heart. Reduction of I to density is consistently observed in human heart failure (HF) and animal HF models. It has been proposed that I to , via its influence on phase‐1 repolarization of the action potential, facilitates L‐type Ca 2+ current (I Ca–L ) activation and sarcoplasmic reticulum Ca 2+ release, and that its down‐regulation may contribute to the impaired contractility in failing heart.Methods and Results:We used the dynamic clamp to quantitatively examine the influence of I to on the mechanical properties of canine left ventricular myocytes at 34°C. In endocardial myocytes, where the native I to is small, simulation of an epicardial‐level artificial I to accentuated the phase‐1 repolarization and significantly suppressed cell shortening. The peak amplitude of Ca 2+ transient was also reduced in the presence of simulated I to , although the rate of rise of the Ca 2+ transient was increased. Conversely, subtraction, or “blockade” of the native I to enhanced contractility in epicardial cells. These results agree with the inverse correlation between I to levels and myocyte contractility and Ca 2+ transient amplitude in epicardial and endocardial myocytes. Action potential clamp studies showed that the phase‐1 repolarization/I to versus I Ca–L relationship had an inverted‐J shape; small I to enhanced peak I Ca–L while moderate‐to‐large I to decreased peak I Ca–L and markedly reduced early Ca 2+ influx.Conclusion:Our results show that epicardial‐level of I to acts as a negative, rather than positive regulator of myocyte mechanical properties in canine ventricular myocytes. (J Cardiovasc Electrophysiol, Vol. 21, pp. 697‐703, June 2010)