lasalocid and Arrhythmias--Cardiac

1. Effects of calcium ionophores (A23187 and X-537A) on the spontaneously beating sino-atrial (SA) node cells of rabbit heart were examined using electron microscopic and an electrophysiological techniques. 2. During exposure to A23187 or X-537A (2 x 10(-5) M), the cycle length was significantly prolonged by 11% (n = 12) or 118% (n = 11), respectively. But neither ionophore affected other action potential parameters. 3. X-537A (2 x 10(-5) M) induced irregular rhythm (dysrhythmia), probably due to cellular calcium overload. Similarly, ouabain (3 x 10(-7) M) also elicited dysrhythmia. In the presence of isoproterenol (ISP, 10(-7) M), X-537A potentiated dysrhythmia, and A23187 newly induced it. 4. In ultrastructural analyses, X-537A caused swelling of the cisternae of Golgi apparatus within 10 min, whereas A23187 and ouabain did not produce any changes even after 30 min-application. 5. Addition of high Ca2+ (10 mM) and/or ISP (10(-7) M) to X-537A produced a further dilation and vacuolization. In A23187 or ouabain, however, the addition of Ca2+ and ISP did not cause any changes, even during dysrhythmia. 6. These results indicate that X-537A elicited a more potent calcium overload than A23187, and that a discrepancy between ultrastructural damages and electrical changes exists.

Topics: Animals; Arrhythmias, Cardiac; Calcimycin; Electrophysiology; In Vitro Techniques; Isoproterenol; Lasalocid; Microscopy, Electron; Ouabain; Rabbits; Sinoatrial Node

Electrophysiological effects of calcium ionophores, A23187 and X-537A, on spontaneously beating and voltage-clamped rabbit sino-atrial node preparations were examined, using the voltage-clamp technique with two microelectrodes. (1) A23187 (administered cumulatively) increased the cycle length significantly at 3 x 10(-6) and 10(-5) mol/l, and X-537 only at 10(-5) mol/l. Other action potential parameters were unaffected in the presence of these concentrations of either agent. At 2 x 10(-5) mol/l, either agent prolonged the cycle length significantly, but increased the amplitude and the duration of the action potentials and the maximum diastolic potential not to any significant extent. Both X-537A and A23187, at 2 x 10(-5)mol/l, induced a dysrhythmia, which in the former was probably due to delayed afterdepolarizations. (2) In voltage-clamped sino-atrial node cells, the holding current was shifted outwardly, to a greater extent in the presence of X-537A than A23187 at the same concentration (2 x 10(-5) mol/l). The ionophores initially increased the slow inward current and then decreased it. The steady outward current was inhibited, and its activation curve was shifted to a more negative voltage range. X-537A caused a transient inward current and an inward tail current on repolarization to the holding potential. (3) At concentrations of 10 and 18 mmol/l [Ca2+]o or in the presence of isoprenaline 10(-7) mol/l, these ionophores induced a more severe dysrhythmia. Conversely in the nominal absence of [Ca2+]o the regular rhythm was resumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Calcimycin; Calcium; Electrophysiology; In Vitro Techniques; Isoproterenol; Lasalocid; Membrane Potentials; Rabbits; Sinoatrial Node

In high concentrations, the ionophores salinomycin, monensin and X-537A cause cardiac arrhythmias in vivo. To determine if these arrhythmias result from a direct action of these ionophores on cardiac electrophysiology, we studied their effects on automaticity and transmembrane action potentials of isolated canine left ventricular Purkinje fibers. High concentrations of the ionophores suppressed automaticity and shortened action potential duration. These data suggest that high concentrations of the ionophores provoke cardiac arrhythmias in vivo by similar mechanisms despite their diverse cation transport selectivities.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Cations; Dogs; Heart Rate; Ionophores; Lasalocid; Monensin; Nadolol; Propanolamines; Purkinje Fibers; Pyrans