Effects of changes in external calcium concentration and frequency of stimulation on inotropic responses to isoprenaline and tolbutamide in rabbit atria.

1. Driven left atrial preparations were used to study inotropic responses to isoprenaline and tolbutamide. 2. Decreasing the external calcium concentration from 2.2 to 1.1 and 0.55 mM decreased resting force of contraction but increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50 values. 3. Decreasing the external calcium concentration from 2.2 to 1.1 mM also increased the maximal inotropic responses to tolbutamide. These responses were 23- and 44-fold less than those to isoprenaline at equivalent calcium concentrations. 4. Preparations maintained in 1.1 mM calcium were used to compare inotropic responses to isoprenaline and tolbutamide at different frequencies of stimulation. 5. Decreasing the frequency of stimulation from 4 to 2 or 1 Hz decreased the resting force of contraction and increased the maximal inotropic responses to isoprenaline. There was an associated increase in EC50 values. 6. No significant inotropic responses to tolbutamide were observed at 4 Hz. Positive inotropic responses of similar magnitude occurred at 2 and 1 Hz. The maximal inotropic responses at these frequencies were 43- and 127-fold less than those to isoprenaline. 7. It is concluded that tolbutamide is a very weak inotropic agent.