Characterization of junctional sarcoplasmic reticulum Ca2+ content and release by short-term mechanical restitution in cardiac muscle.
To study Ca2+ handling by the junctional sarcoplasmic reticulum (JSR), the time course of short-term mechanical restitution after varying magnitudes of twitch contractions was assessed in rat papillary muscle. Mechanical restitution consisted of a pretwitch latency period followed by a rapid and a subsequent much slower restitution of twitch force. The rate of rapid restitution was independent of the magnitude of the preceding twitch, which suggests that the rate of JSR Ca2+ repletion was dependent on the amount of Ca2+ remaining in the JSR after a twitch contraction. Based on this finding, the functions Gt and Ht, representing the time courses of JSR Ca2+ repletion and release, respectively, were derived graphically from a family of the mechanical restitution curves. Gt increased monotonically with time at a decreasing rate, while Ht increased with time in a sigmoid manner. The mechanical alternans were simulated by using experimental values and mathematically predicted values of Gt and Ht. A substitution of extracellular Na+ with Li+ to inhibit Na+/Ca2+ exchange resulted in an augmentation of Gt by approximately 10%, presumably by increasing the tubular SR Ca2+ uptake. The inhibition of tubular SR Ca2+ uptake by thapsigargin (10 microM) reduced mechanical restitution by approximately 13% of the maximal twitch force, independent of the phase of mechanical restitution; the effect was greater at an earlier time point in the mechanical restitution. These results suggest that early JSR Ca2+ replenishment results mainly from the movement of Ca2+ from the tubular SR.
Tameyasu
T
T
Department of Physiology, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, 216-8511 Japan. t2tame@marianna-u.ac.jp
Tanaka
M
M
Ogura
S
S
Sato
M
M
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D066298:In Vitro Techniques; D008297:Male; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D013314:Stress, Mechanical; D019284:Thapsigargin / Q000494:pharmacology
D019831:Sodium-Calcium Exchanger; D019284:Thapsigargin; D002118:Calcium