Cellular mechanisms for the slow phase of the Frank-Starling response

Citation
Wf. Bluhm et al., Cellular mechanisms for the slow phase of the Frank-Starling response, J ELCARDIOL, 31, 1998, pp. 13-22
Citations number
48
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
JOURNAL OF ELECTROCARDIOLOGY
ISSN journal
00220736 → ACNP
Volume
31
Year of publication
1998
Supplement
S
Pages
13 - 22
Database
ISI
SICI code
0022-0736(1998)31:<13:CMFTSP>2.0.ZU;2-6
Abstract
Following a step increase in sarcomere length, isometric cardiac muscle ten sion increases instantaneously by the Frank-Starling mechanism. Ln isolated papillary muscle and myocytes, there is an additional significant rise in developed tension over the following 15 min due to an unknown mechanism. Th is slow change in tension could not be explained by mechanical heterogeneit y of the muscle preparations or by an increase in myofilament sensitivity t o Ca2+. The slow change in tension was not dependent on sarcoplasmic reticu lum Ca2+ loading assessed with rapid cooling contractures, and was not sign ificantly altered by sarcoplasmic reticulum Ca2+ depletion (ryanodine) or i nhibition of sarcoplasmic reticulum Ca2+ reuptake (cyclopiazonic acid). We used the Luo-Rudy ionic model of the ventricular myocyte together with a mo del of the length-dependent myofilament activation by Ca2+ to examine the e ffects of step changes in the parameters of sarcolemmal ion fluxes as possi ble mechanisms for the slow change in stress. The slow increase in tension was simulated by step changes in the Na+-K+ pump or Na+ leak currents, sugg esting that the slow change in stress may be caused by length induced chang es in Na+ fluxes. The model also predicted a slow increase in the magnitude of the initial repolarization during phase 1 of the action potential. The combination of experimental and computational models used in this investiga tion represents a valuable technique in elucidating the cellular mechanisms of fundamental processes in cardiac excitation-contraction coupling.