Received March 26, 2007
Revised May 2, 2007
Accepted after revision June 14, 2007
Heart/Cardiac Muscle [240]
|
Temporal variability of repolarization in rat ventricular myocytes paced with time-varying frequencies
Massimiliano Zaniboni 1*,
Francesca Cacciani 1,
Nicolò Salvarani 1
1 Universitá degli Studi di Parma
* To whom correspondence should be addressed. E-mail: zaniboni{at}biol.unipr.it.
 |
Abstract |
|---|
Adaptation of action potential duration (APD) to pacing cycle length (CL) has been previously characterized in isolated cardiomyocytes for sudden changes in constant CL and for pre/post-mature stimuli following constant pacing trains. However, random fluctuations characterize both physiological sinus rhythm (up to 10% of mean CL) and intrinsic beat-to-beat APD at constant pacing rate. We analyzed the beat-to-beat sensitivity of each APD to the preceding CL during constant-sudden, random, or linearly changing pacing trains in single patch clamped rat left ventricular myocytes, in the absence of autonomic and electrotonic effects which modulate rate-dependency in intact heart. Beat-to-beat variability of APD at -60 mV, quantified as SD over 10-beats sequences, increased with corresponding mean APD. When measured as coefficient of variability CV, APD-60mV variability was inversely proportional to pacing frequency (from 1.2% at 5 Hz to 3.2% at 0.2 Hz), it was increased, at a basic CL (BCL) of 250 ms, by 55% by the L-type calcium current (ICaL) blocker nifedipine, and decreased by 23% by the transient-outward potassium current (Ito) blocker 4-aminopyridine. APD variability at BCL = 250 ms prevented detecting random changes of CL smaller than ~ 5%. Ten percent random changes in CL were detected as a 40% increase in CV of APD and tended to correlate with it (R = 0.43). ICaL-block depressed this correlation (R = 0.23) whereas Ito-block significantly increased it (R = 0.67); similarly with linearly changing CL ramps (ranging ± 10% and ±; 20% of 250 ms). We conclude that beat-to-beat APD variability, a major determinant of propensity to arrhythmia development in the heart, is present in isolated myocytes, where it is APD- and rate-dependent. APD shows a beat-to-beat positive correlation with preceding randomly/linearly changing CL, which can be pharmacologically modulated.
Key Words:
Action potential, Cardiac cell, Electrophysiology
