Sarcoplasmic reticulum and Na+/Ca2+ exchanger function during early and late relaxation in ventricular myocytes.
The relative importance of the Na+/Ca2+ exchanger in the initial and terminal phases of relaxation and the decline in the [Ca2+]i transient was investigated in adult rabbit ventricular myocytes loaded with the Ca2+ indicator fluo 3. For electrically stimulated contractions, the peak intracellular Ca2+ concentration ([Ca2+]i) was 700 +/- 87 nM and end-diastolic [Ca2+]i was 239 +/- 30 nM (0.25 Hz, 37 degrees C, 1.08 mM extracellular Ca2+ concentration; n = 14). Abrupt inhibition of Na+/Ca2+ exchange was produced by removal of extracellular Na+ (KCl substitution) and Ca2+ [2 mM Ca(2+)-free ethylene glycol-bis(beta-aminoethyl either)-N,N,N',N'-tetraacetic acid] by means of a rapid switcher device (SW). Abrupt exposure to high K+ induced an action potential, although sufficient Ca2+ remained adjacent to the sarcolemma to induce a contraction (SW beat) and [Ca2+]i transient that were identical in amplitude to those induced by electrical stimulation (ES beat). The initial relaxation and decline in the [Ca2+]i transient was not significantly prolonged by abrupt elimination of the Na+/Ca2+ exchanger, but the rate and extent of the terminal phase of the decline in the [Ca2+]i transient were significantly reduced. The first derivative of [Ca2+]i with respect to time versus [Ca2+]i during the decline of the [Ca2+]i transient attributable to sarcoplasmic reticulum (SR) function was estimated from the average SW transients, and that attributable to Na+/Ca2+ exchange was estimated from the difference between SW and ES transients. By this analysis, the Na+/Ca2+ exchanger produces 13% of the first half of the decline in [Ca2+]i and 45% of the second half of the decline. We conclude that abrupt inhibition of forward Na+/Ca2+ exchange does not significantly affect the amplitude or the initial rate of decline of the [Ca2+]i transient and relaxation. However, its contribution to the reduction of [Ca2+]i becomes apparent late during the [Ca2+]i transient, when cytosolic [Ca2+]i has been reduced.
Yao
A
A
Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Matsui
H
H
Spitzer
K W
KW
Bridge
J H
JH
Barry
W H
WH
D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003971:Diastole; D005456:Fluorescent Dyes; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D014664:Vasodilation; D014966:Xanthenes
D000814:Aniline Compounds; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D014966:Xanthenes; C059715:Fluo-3; D012964:Sodium; D011188:Potassium; D002118:Calcium