Morphological and electrophysiological changes induced by calcium ionophores (A23187 and X-537A) in spontaneously beating rabbit sino-atrial node cells

Abstract

1. 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. 2. During exposure to A23187 or X-537A (2 × 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. 3. X-537A (2 × 10 −5 M) induced irregular rhythm (dysrhythmia), probably due to cellular calcium overload. Similarly, ouabain (3 × 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. 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. 5. Addition of high Ca 2+ (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 Ca 2+ and ISP did not cause any changes, even during dysrhythmia. 6. 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.