title: Excitation-contraction coupling in human heart failure examined by action potential clamp in rat cardiac myocytes.
abstract: The effect of the loss of the notch in the human action potential (AP) during heart failure was examined by voltage clamping rat ventricular myocytes with human APs and recording intracellular Ca(2+) with fluorescent dyes. Loss of the notch resulted in about a 50% reduction in the initial phase of the Ca(2+) transient due to reduced ability of the L-type Ca(2+) channel to trigger release. The failing human AP increased non-uniformity of cytosolic Ca(2+), with some cellular regions failing to elicit Ca(2+)-induced Ca(2+) release from the sarcoplasmic reticulum. In addition, there was an increase in the occurrence of late Ca(2+) sparks. Monte-Carlo simulations of spark activation by L-type Ca(2+) current supported the idea that the decreased synchrony of Ca(2+) spark production associated with the loss of the notch could be explained by reduced Ca(2+) influx from open Ca(2+) channels. We conclude that the notch of the AP is critical for efficient and synchronous EC coupling and that the loss of the notch will reduce the SR Ca(2+) release in heart failure, without changes in (for example) SR Ca(2+)-ATPase uptake.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Cooper
authors.forename: Christian
authors.initials: C
authors.lastname: Soeller
authors.forename: Mark B
authors.initials: MB
authors.lastname: Cannell
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003198:Computer Simulation; D056966:Excitation Contraction Coupling / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D009010:Monte Carlo Method; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium