The mechanism of the increase of tonic tension produced by caffeine in sheep cardiac Purkinje fibres.

Abstract

The effects of caffeine were examined on contraction and membrane current in voltage-clamped sheep cardiac Purkinje fibers. The photoprotein aequorin was injected into several cells to measure the intracellular ionized Ca concentration ([Ca2+]i). When the Na-K pump was inhibited, depolarization produced a twitch followed by a topic component of tension. Repolarization produced an after-contraction. These components of tension were accompanied by corresponding increases of aequorin light. Caffeine (10 mM) decreased the twitch and the after-contraction while increasing the tonic component. The application of caffeine also produced a transient increase of aequorin light, during depolarization and at rest, which was followed by a maintained decrease in all 3 components of the light signal. Although caffeine decreased the rise of aequorin light during prolonged depolarization it increased the tonic tension. The possibility that the effects of caffeine on tonic tension could be due to suppression of spontaneous Ca oscillations was rejected for the following reasons. Ryanodine (which also abolishes Ca oscillations) decreased the magnitude of the tonic tension. Caffeine still increased tonic tension when it was added to a fiber exposed to ryanodine (1-10 .mu.M). With ryanodine it was possible to measure [Ca2+]i and tonic tension without interference from Ca oscillations. The increase of tonic tension produced by caffeine could not be accounted for by a rise of [Ca2+]i. At a given level of Ca, caffeine evidently increased tension. A large part of the increase in tonic tension produced by caffeine is due to an increase of the Ca sensitivity of the contractile apparatus rather than to changes of [Ca2+]i. The consequence of this observation for the experimental use of caffeine is discussed.