Does adrenaline modulate the Na+-Ca2+ exchanger in isolated toad pacemaker cells?

beta-Adrenergic stimulation of pacemaker cells from the sinus venosus of the cane toad (Bufo marinus) increases intracellular calcium ([Ca2+](i)) and firing rate. The increase in [Ca2+](i) could contribute to the increased firing rate by increasing the inward Na+-Ca2+ exchange current (INa-Ca) during diastole. In this study we measured [Ca2+](i) and membrane currents in single, isolated, voltage-clamped pacemaker cells. We show that INa-Ca increases during beta-adrenergic stimulation. To test whether this increase in INa-Ca is caused by elevated [Ca2+](i) or by changes in the properties of the Na+-Ca2+ exchanger, we made rapid applications of caffeine and plotted the INa-Ca against [Ca2+](i). This relationship was linear during the declining phase of the [Ca2+](i) signal caused by caffeine and was not significantly different in the presence or absence of beta stimulation. These results show that INa-Ca is increased during beta-adrenergic stimulation and will contribute to the increased firing rate. However the increase in INa-Ca appears to be a consequence of the increase in [Ca2+](i) and is not caused by changes in the intrinsic properties of the Na+-Ca2+ exchanger.