Abstract(#br)The role of intracellular sodium activity (a Na i ) in the control of force was studied in sheep cardiac Purkinje fibers exposed to norepinephrine (NE) and high [Ca] o in the absence and presence of overdrive or of a low concentration of strophanthidin. Both NE and high [Ca] o decrease a Na i and increase force, while overdrive increases and low strophanthidin decreases both parameters. In the presence of NE, overdrive increases a Na i less than force and is followed by a more pronounced undershoot in a Na i and force. In contrast, in high [Ca] o overdrive increases a Na i more than force and is followed by a less pronounced undershoot in a Na i and force than in NE. High [Ca] o increases force to a peak, but then the decreasing a Na i reduces force. In all these conditions,... a Na i determines force changes during recovery from overdrive. NE and high [Ca] o decrease a Na i less and increase force more in low strophanthidin. Thus, changes in a Na i modulate the increase in force due to increased Ca influx and control force development when Ca influx is either unchanged (low strophanthidin) or has reached a steady state (high [Ca] o , recovery from overdrive).