Contraction in cardiac muscle is initiated by an increase in [Ca²⁺]_i and relaxation occurs as [Ca²⁺]_i is lowered through a combination of re-uptake into the sarcoplasmic reticulum (SR) and extrusion across the sarcolemma by the Na⁺-Ca²⁺ exchanger and sarcolemmal Ca²⁺-ATPase. These mechanisms have been well characterized in the ventricle, although in atrial muscle such information is lacking.

The aim of the current experiments was to determine the relative roles of the SR and sarcolemmal mechanisms in the removal of calcium from the cytoplasm of atrial myocytes. Figure 1 illustrates the experimental approach that was used. Cells were isolated from rats and ferrets killed by pentobarbitone overdose and stimulated using field electrodes or voltage clamp pulses (23 °C, 1 mM external Ca²⁺) until a steady-state Ca²⁺ transient was reached. Stimulation was then stopped and 10 mM caffeine added. Caffeine discharges the SR store and under these conditions prevents effective Ca²⁺ uptake by the SR. After the caffeine-evoked Ca²⁺ transient had decayed, the caffeine was removed and stimulation resumed. Once the Ca²⁺ transient had recovered, 10 mM Ni²⁺ was added to the cell to block the Na⁺-Ca²⁺ exchanger before caffeine was again added to release Ca²⁺.

On average in rat atrial myocytes (n = 15) caffeine slowed the rate of decay of [Ca²⁺]_i to 7.7 ± 0.9 % (S.E.M.) of the control systolic Ca²⁺ transient, suggesting that the SR is responsible for 92 % of the total Ca²⁺ extrusion from the cytoplasm. Ni²⁺, which was used to block the Na⁺-Ca²⁺ exchanger, slowed the caffeine-evoked Ca²⁺ transient by 85 ± 2 %, suggesting that in atrial cells the exchanger is responsible for removing this fraction of the non-SR component of total Ca²⁺. Quantitatively similar results were obtained in ferret atrial myocytes (n = 8, 7.5 ± 1 and 84 ± 3 %). These results should be compared with data from rat and ferret ventricular myocytes which suggest that, although the SR makes a similar contribution to total Ca²⁺ extrusion (90 %) (Negretti et al. 1993; Trafford et al. 1997), the Na⁺-Ca²⁺ exchange accounts for a smaller fraction of the non-SR-dependent Ca²⁺ removal (65 %).

Figure 1. Measurement of [Ca2+]i in ferret atrial myocytes. A, time course. The cell was stimulated using voltage-clamp pulses. Stimulation was stopped and Ni2+ and caffeine applied as indicated. B, normalised records shown on an expanded timescale.

Negretti, N., O’Neill, S.C. & Eisner, D.A. (1993). Cardiovasc. Res. 27, 1826-1830.

Trafford, A.W., DÆaz, M.E., Negretti, N. & Eisner, D.A. (1997). Circ. Res. 81, 477-484.