Effects of β‐Adrenergic Receptor Activation on Intracellular Calcium and Membrane Potential in Adult Cardiac Myocytes

β‐Adrenergic Receptor Activation and Intracellular Ca 2+ . Introduction: β‐Adrenergic receptor agonists have been shown to increase the voltage‐dependent Ca 2+ current in cardiac myocytes. Additionally, adrenergic receptor activation has been shown to increase intracellular Ca 2+ , to increase systolic Ca 2+ transients and to enhance Ca 2+ uptake into the sarcoplasmic reticulum, thereby accelerating relaxation. The present study was designed first to characterize the influences of β‐adrenergic receptor activation on intracellular Ca 2+ activity as well as membrane potential in ventricular myocytes characterized as normal based on rigorous morphologic and electrophysiologic criteria. The second objective was to assess whether the increase in intracellular Ca 2+ activity elicited by β‐adrenergic receptor activation could elicit afterdepolarizations and triggered activity. Methods and Results: Intracellular Ca 2+ and whole‐cell voltage recordings were measured in cells in which indo‐1 free acid was delivered intracellularly through the recording pipette. Isoproterenol produced complex Ca 2+ transients underlying both early and delayed afterdepolarizations during pacing as well as aftertransients underlying triggered action potentials and delayed afterdepolarizations in the absence of pacing. The coupling interval of Ca 2+ i aftertransients was frequency dependent and followed that of the delayed afterdepolarizations. Ca 2+ i after transient amplitudes, however, exhibited a biphasic response with frequency revealing that factors other than pacing frequency alone contribute to control of the amplitude of the aftertransients. Inhibition of sarcoplasmic reticular release of Ca 2+ by ryanodine abolished Ca 2+ i aftertransients and afterdepolarizations otherwise elicited by isoproterenol. Conclusion: These data demonstrate that normal cells stimulated by β‐adrenergic agonists exhibit marked changes in intracellular Ca 2+ homeostasis that may serve as the substrate for abnormal ion fluxes that ultimately contribute to electrophysiologic derangements underlying arrhythmogenesis in the intact heart. ( J Cardiovasc Electrophysiol, Vol. 3, pp. 209–224, June 1992 )