Allosteric activation of Na+-Ca2+ exchange by L-type Ca2+ current augments the trigger flux for SR Ca2+ release in ventricular myocytes.
The possible contribution of Na(+)-Ca(2+) exchange to the triggering of Ca(2+) release from the sarcoplasmic reticulum in ventricular cells remains unresolved. To gain insight into this issue, we measured the "trigger flux" of Ca(2+) crossing the cell membrane in rabbit ventricular myocytes with Ca(2+) release disabled pharmacologically. Under conditions that promote Ca(2+) entry via Na(+)-Ca(2+) exchange, internal [Na(+)] (10 mM), and positive membrane potential, the Ca(2+) trigger flux (measured using a fluorescent Ca(2+) indicator) was much greater than the Ca(2+) flux through the L-type Ca(2+) channel, indicating a significant contribution from Na(+)-Ca(2+) exchange to the trigger flux. The difference between total trigger flux and flux through L-type Ca(2+) channels was assessed by whole-cell patch-clamp recordings of Ca(2+) current and complementary experiments in which internal [Na(+)] was reduced. However, Ca(2+) entry via Na(+)-Ca(2+) exchange measured in the absence of L-type Ca(2+) current was considerably smaller than the amount inferred from the trigger flux measurements. From these results, we surmise that openings of L-type Ca(2+) channels increase [Ca(2+)] near Na(+)-Ca(2+) 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 Ca(2+) release in heart cells under various conditions.
Sobie
Eric A
EA
Cannell
Mark B
MB
Bridge
John H B
JH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology; D015640:Ion Channel Gating / Q000502:physiology*; D032383:Myocytes, Cardiac; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D016276:Ventricular Function
D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium