Electrophysiological actions of A23187 and X-537A in spontaneously beating and in voltage-clamped rabbit sino-atrial node preparations

Abstract

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)