Ca2+ waves during triggered propagated contractions in intact trabeculae. Determinants of the velocity of propagation.
During triggered propagated contractions, Ca2+ waves travel along cardiac trabeculae with a constant velocity (Vprop) ranging from 0. 34 to 5.47 mm/s. To explore the determinants of Vprop, we studied (1) the relationship between [Ca2+]i and Vprop and (2) the effect of low concentrations of caffeine on Vprop. Trabeculae were dissected from the right ventricle of rat hearts. [Ca2+]i was measured using electrophoretically injected fura-2 and an image-intensified CCD camera. Force was measured using a silicon strain gauge, and sarcomere length was measured using laser diffraction techniques. After induction of reproducible Ca2+ waves by trains of electrical stimuli (2.5 Hz) at 21.9+/-0.2 degrees C, the number of stimuli or [Ca2+]o was varied in 9 trabeculae. In 5 trabeculae, the effects of caffeine (0.1 to 1.0 mmol/L) at [Ca2+]o of 2.2+/-0.3 mmol/L were determined. All images were recorded under stable conditions of wave propagation. The increment in [Ca2+]i during the last electrically stimulated transient (DeltaCaT) and [Ca2+]i just before onset of the Ca2+ waves (CaD) were used to estimate the Ca2+ loading of the sarcoplasmic reticulum (SR) and the myoplasm, respectively. The ratio (DeltaCaW/DeltaCaT) of the [Ca2+]i increment during the waves (DeltaCaW) to DeltaCaT was used to estimate the probability of opening of the SR-Ca2+ release channel during wave propagation. As a result of an increase of the number of stimuli or [Ca2+]o, Vprop increased in proportion to (1) DeltaCaT (r=0.82); (2) CaD (r=0.88); (3) DeltaCaW (r=0.85); and (4) DeltaCaW/DeltaCaT (r=0.74). The addition of caffeine (</=0.3 mmol/L) increased Vprop for any DeltaCaT and any DeltaCaW, revealing an increased sensitivity of Vprop to DeltaCaT and DeltaCaW. In contrast, caffeine had little effect on the relationship between Vprop and CaD and no effect on that between Vprop and DeltaCaW/DeltaCaT. These results suggest that both the cellular Ca2+ loading and open probability of the SR-Ca2+ release channels determine the velocity of propagation of Ca2+ waves.
Miura
M
M
Department of Medicine, University of Calgary, Calgary, Canada.
Boyden
P A
PA
ter Keurs
H E
HE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes; D016257:Fura-2; D007700:Kinetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010507:Periodicity; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D002118:Calcium; D016257:Fura-2