Control of interval-force relation in canine ventricular myocardium studied with ryanodine.

1. The mechanism of post-extrasystolic, rest and frequency potentiation was studied in canine isolated ventricular muscle. 2. Ryanodine, which impairs Ca availability from the sarcoplasmic reticulum (SR), reduced the amplitude of the extrasystole less than that of the steady state contraction. Ryanodine also inhibited post-extrasystolic potentiation and converted rest-potentiation into rest depression. Rest-potentiation was blocked preferentially by ryanodine compared to post-extrasystolic potentiation. An increase in the contribution of extracellular Ca to the extrasystolic contraction could not entirely account for the post-extrasystolic potentiation. 3. Prolonged rest, by itself, also caused depression of the first post-rest contraction. During rest-potentiation, SR Ca seemed to play a greater role in contraction than transmembrane Ca influx. However, the ability of the 'release pool' of Ca in the SR to be reprimed after a contraction was reduced. This was seen as a decrease in post-extrasystolic potentiation elicited immediately after rest. 4. A decrease in stimulus interval was associated with a transient decrease in contraction amplitude followed by an increase. An abrupt increase in stimulus interval had the opposite effect. Ryanodine blocked the initial transient changes and accelerated the delayed changes. These results suggest that the transient changes in contraction after sudden changes in drive interval are dependent on the SR. 5. Transmembrane Ca entry and the rate of recovery of the Ca release process (repriming) in the SR after a contraction seem to be interval-dependent. The data also indicate that different mechanisms are involved in post-extrasystolic and rest-potentiation. 6. The results are consistent with a model which proposes 'recirculation' of activator Ca within the SR after a contraction or of the presence of an appreciable amount of inactivation of the SR Ca release process during normal stimulation. An increased pool of releasable Ca due to longer recirculation time or a time-dependent decay in the level of inactivation of Ca release from the SR may give rise to rest-potentiation.