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This Article Full Text Full Text (PDF) All Versions of this Article: 92/5/859    most recent expphysiol.2007.037986v1 Alert me when this article is cited Alert me if a correction is posted 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 Google Scholar Google Scholar Articles by Zaniboni, M. Articles by Salvarani, N. Search for Related Content PubMed PubMed Citation Articles by Zaniboni, M. Articles by Salvarani, N.

¹ Dipartimento di Biologia Evolutiva e Funzionale – Sezione Fisiologia, Università degli Studi di Parma, Viale G.P. Vsberti 11/A, 43100 Parma, Italy

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-/postmature 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 analysed 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 the autonomic and electrotonic effects that modulate rate dependency in the intact heart. Beat-to-beat variability of APD at –60 mV (APD_{–60 mV}), quantified as S.D. over 10-beat sequences, increased with corresponding mean APD. When measured as coefficient of variability (CV), APD_{–60 mV} 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 (I_CaL) blocker nifedipine, and decreased by 23% by the transient-outward potassium current (I_to) blocker 4-aminopyridine. Variability of APD at BCL of 250 ms prevented the detection of random changes of CL smaller than 5%. Ten per cent random changes in CL were detected as a 40% increase in CV of APD and tended to correlate with it (r = 0.43). Block of I_CaL depressed this correlation (r = 0.23), whereas block of I_to significantly increased it (r = 0.67); this was similar with linearly changing CL ramps (ranging ±10% and ±20% of 250 ms). We conclude that beat-to-beat APD variability, a major determinant of the propensity for development of arrhythmia in the heart, is present in isolated myocytes, where it is dependent on mean APD and pacing rate. Action potential duration shows a beat-to-beat positive correlation with preceding randomly/linearly changing CL, which can be pharmacologically modulated.

(Received 26 March 2007; accepted after revision 14 June 2007; first published online 15 June 2007)
Corresponding author M. Zaniboni: Dipartimento di Biologia Evolutiva e Funzionale – Sezione Fisiologia, Università degli Studi di Parma, Viale G.P. Usberti 11A, 43100 Parma, Italy. Email: zaniboni{at}biol.unipr.it