Allosteric Activation of Na-Ca Exchange by L-Type Ca Current Augments the Trigger Flux for SR Ca Release in Ventricular Myocytes |
| |
Authors: | Eric A Sobie John HB Bridge |
| |
Institution: | * Department of Pharmacology & Systems Therapeutics, Mount Sinai School of Medicine, New York, New York † Department of Physiology, University of Auckland, Auckland, New Zealand ‡ Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah |
| |
Abstract: | The possible contribution of Na+-Ca2+ exchange to the triggering of Ca2+ release from the sarcoplasmic reticulum in ventricular cells remains unresolved. To gain insight into this issue, we measured the “trigger flux” of Ca2+ crossing the cell membrane in rabbit ventricular myocytes with Ca2+ release disabled pharmacologically. Under conditions that promote Ca2+ entry via Na+-Ca2+ exchange, internal Na+] (10 mM), and positive membrane potential, the Ca2+ trigger flux (measured using a fluorescent Ca2+ indicator) was much greater than the Ca2+ flux through the L-type Ca2+ channel, indicating a significant contribution from Na+-Ca2+ exchange to the trigger flux. The difference between total trigger flux and flux through L-type Ca2+ channels was assessed by whole-cell patch-clamp recordings of Ca2+ current and complementary experiments in which internal Na+] was reduced. However, Ca2+ entry via Na+-Ca2+ exchange measured in the absence of L-type Ca2+ current was considerably smaller than the amount inferred from the trigger flux measurements. From these results, we surmise that openings of L-type Ca2+ channels increase Ca2+] near Na+-Ca2+ exchanger molecules and activate this protein. These results help to resolve seemingly contradictory results obtained previously and have implications for our understanding of the triggering of Ca2+ release in heart cells under various conditions. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|