Calcium Transients in Infant Human Atrial Myocytes

Abstract

Isolated infant human atrial cells have a slower early repolarization than adult human atrial cells. In addition, from room temperature voltage-clamp studies, infant cells have lower basal L-type calcium currents than adult cells. We hypothesized that the slower repolarization increases the calcium transient of infant human atrial cells. Atrial myocytes were enzymatically dissociated from biopsies of human right atrial appendages of infant (3-8 mo) patients who were undergoing open-heart surgery. Intracellular calcium transients were measured with fluorescence microscopy with application of either square waves or action potential waveforms at physiologic temperature. After repetitive application (1 Hz) of 100-ms duration conditioning depolarizations to 10 mV (from Ϫ80 mV), a test pulse of varying duration (⌬T; 2-100 ms) produced smaller transients (expressed as percentage of the last conditioning pulse) at shorter durations (33 Ϯ 7% for ⌬T ϭ 2 ms, 80 Ϯ 4% for ⌬T ϭ 25 ms). The time course and amplitude of the calcium current, which leads via sarcoplasmic reticulum (SR) calcium release to the calcium transient of cardiac cells, depend not only on the properties of the calcium channel but also on the action potential waveform. Changes in the action potential repolarization rate have been shown to have effects to either increase or decrease the net calcium current and the release of calcium from the SR (1-3). In our recent work comparing action potential waveforms and the amplitude and time course of transient outward current in isolated infant versus adult human atrial cells (4), we showed 1) that infant atrial cells had transient outward current that inactivated much more rapidly than adult atrial cells and 2) that infant cells had a much slower early repolarization phase [consistent with previous work on atrial strips (5)]. The time for 30% repolarization from the peak of the action potential (APD 30 ) was 24.4 Ϯ 11.4 ms for infant atrial cells compared with only 3.6 Ϯ 0.4 ms for adult atrial cells. We have also shown that infant cells have a lower basal amplitude of calcium current than do either young adult or older adult atrial cells (6), with peak L-type calcium current (I Ca ) from voltage steps to 10 mV at room temperature being 1.2 Ϯ 0.1 pA/pF for infant cells and 2.6 Ϯ 0.3 pA/pF for adult cells.The lower I Ca (from square wave voltage-clamp studies) and the prolonged early repolarization phase of the infant atrial cells (from current clamp single-cell studies) may be related in a functional sense if the prolongation of the early repolarization served to increase the calcium entry and thus the intracellular calcium transient in infant atrial cells compared with the faster

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Difference of Sodium Currents between Pediatric and Adult Human Atrial Myocytes: Evidence for Developmental Changes of Sodium Channels

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Transient outward potassium current and Ca2+ homeostasis in the heart: beyond the action potential

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