Morphological and electrophysiological changes induced by calcium ionophores (A23187 and X-537A) in spontaneously beating rabbit sino-atrial node cells.
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.
Satoh
H
H
Department of Pharmacology, Nara Medical University, Japan.
Uchida
T
T
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology*; D004594:Electrophysiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007832:Lasalocid / Q000494:pharmacology*; D008854:Microscopy, Electron; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure
D000001:Calcimycin; D010042:Ouabain; D007545:Isoproterenol; D007832:Lasalocid