Fig. 1.

Excitation-contraction coupling (ECC) failure by carvedilol. Carvedilol inhibits action potential-induced Ca²⁺ release during ECC. ECC disruption was defined as the inability of electrical filed stimulation (1 Hz) to elicit Ca²⁺ transient (CaTs) in isolated rabbit atrial myocytes. A: representative whole cell intracellular Ca²⁺ concentration ([Ca²⁺]_i) profiles and corresponding line scan images in control (n = 65) and during exposure to 0.5 µM (n = 10 cells), 1 µM (n = 14), 3 µM (n = 21), and 10 µM (n = 20) carvedilol and the negative control with metoprolol (Met; 10 µM, n = 7). Black circles indicate time of electrical stimulus. B: fraction of cells (%) showing ECC disruption. A single failure of Ca²⁺ release during the test period of 10 s counted as a disruption of ECC. C: average CaT amplitudes from control and carvedilol-treated atrial myocytes. The [Ca²⁺]_i responses to 10 consecutive electrical stimulations were averaged, including failures. The Fluo-4 Ca²⁺ signal was averaged over the entire width of the cell. For presentation purposes, control (Ctrl) CaT amplitudes were pooled; however, for statistical analysis (t-test for paired measurements), each carvedilol concentration and the metoprolol group had its own control, since experiments were conducted as a paired measurement with recording control CaTs followed by drug application to the same cell. Means ± SE and individual cell data (white circles) are shown. *P < 0.05. NS, not significant.