title: Ca2+ sparks induced by Na/Ca exchange.
abstract: Whether Ca(2+) influx on the Na/Ca exchanger (NCX) can trigger elementary sarcoplasmic reticulum (SR) Ca(2+) release events (Ca(2+) sparks) is controversial. We imaged [Ca(2+)](i) (Nipkow confocal microscope and fluo-3) in left ventricular myocytes isolated from wild type (WT) and transgenic (TG) mice overexpressing NCX 2.5-fold. Sudden activation of Ca(2+) influx via NCX induced by abrupt exposure to "0" [Na(+)](o)/normal [Ca(2+)](o) solution by means of a rapid solution switcher-induced Ca(2+) sparks in NCX TG myocytes in 425+/-17 ms, n=21. The diameter and amplitude (F/F(0)) of these sparks (2.74+/-0.14 microm, F/F(0)=2.16+/-0.06, n=18) were similar to those induced by field stimulation of myocytes in the presence of 20 microM nifedipine (2.70+/-0.10 microm, F/F(0)=1.98+/-0.08, n=17). In WT myocytes no Ca(2+) sparks were observed within the first 600 ms after abrupt removal of extracellular Na. In parallel experiments, voltage clamp current measurements (-80 mV) showed that the Na/Ca exchange current (I(NCX)) began within 60 ms of activation of the switcher, and peaked at 312+/-57 pA in TG myocytes within 300-500 ms. I(Ca,L) in 20 microM nifedipine was 10.3+/-4.3 pA, n=7. These results indicate that Ca(2+) entering the myocyte via NCX can cause Ca(2+) sparks which are similar to those elicited by electrical stimulation. However, Ca(2+) influx on NCX is much less efficient in inducing Ca(2+) sparks than Ca(2+) influx via I(Ca,L).
authors.affiliation: Division of Cardiology, University of Utah Health Science Center, 50 No. Medical Drive, Salt Lake City, UT 84132, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ritter
authors.forename: Zhi
authors.initials: Z
authors.lastname: Sui
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Philipson
authors.forename: Fenghua
authors.initials: F
authors.lastname: Li
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Spitzer
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishida
authors.forename: William H
authors.initials: WH
authors.lastname: Barry
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004558:Electric Stimulation; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium