Intracellular calcium transients and developed tension in rat heart muscle: A mechanismfor the negative interval-strength relationship

Thepurposes of the present study were to determine (a) whether changes of intracellular [Ca²⁺] (Ca;) can account for the decrease of developed tension observed in rat heart muscle when stimulation rate is increased, and (6) whether the effect of stimulation rate on Ca; is altered in conditions in which the rate of repriming of the sarcoplasmic reticulum (SR) is altered, as when perfusate [Ca²⁺] (Ca₀) is increased, and in heart muscle from senescent animals. The photoprotein aequorin was used to monitor Cai in rat papillary muscles. In muscles from 6-mo-old rats, increasing the stimulation rate in the range 0.2-0.66 Hz led to parallel decreases of both the aequorin light transient and developed tension when Cao was 2 mM. When Ca₀ was increased to 4 mM, changes in the stimulation rate had less effect on both the light transient and tension. At 8 mM Ca₀ changing the stimulation rate had no effect on either the light transient or developed tension. Papillary muscles from 24-mo-old rats, in which SR function is likely to be depressed, exhibited a prolonged Ca21 transient and twitch. At a Ca of 4 or 8 mM, increasing the stimulation rate from 0.33 to 0.66 Hz still led to decreases in the size of the aequorin light transient and developed tension in these muscles. Developed tension and aequorin light responded to increases of Ca₀ in the same way in both groups of muscles. We conclude that under the conditions of our experiments, developed tension is determined by Ca₀. The negative interval-strength relationship observed when Ca₀ is in the physiological range can be accounted for by a timedependent recycling of Ca²⁺ by the SR. The effects of increasing Ca₀ and the age-related differences observed at high Ca₀ can also be accounted for using this model.