Contribution of reverse-mode sodium-calcium exchange to contractions in failing human left ventricular myocytes.
OBJECTIVE
To examine the contribution of reverse mode sodium-calcium (Na-Ca) exchange to contractions in isolated left-ventricular myocytes from failing human heart.


METHODS
Low resistance patch pipettes were used to dialyze cells with Na-free or high-Na pipette solution ([Na]pipette = 0 and 20 mmol/L, respectively) to reduce or enhance Na-Ca exchange. Whole-cell membrane-potential, membrane-current and cell-shortening data were simultaneously acquired during whole-cell voltage clamp protocols. Thapsigargin (100 nmol/L) and nifedipine (1 mumol/L) were also used to inhibit sarcoplasmic reticulum (SR) Ca-ATPase and L-type Ca channels, respectively.


RESULTS
Two types of contractions were observed. Rapid phasic contractions were seen in both Na-free and high-Na cells. Slow tonic contractions were seen only in high-Na cells. Phasic contractions demonstrated bell-shaped voltage dependence over the voltage range that corresponds to the activity of the L-type Ca channel. Although the voltage dependence of phasic contractions were similar Na-free and high-Na cells, phasic contractions in high-Na cells were larger than phasic contractions in Na-free cells. Phasic contractions were sensitive to inhibition of SR Ca-ATPase and L-type Ca channels. Tonic contractions were not inhibited by either thapsigargin or nifedipine. In thapsigargin-treated high-Na cells, tonic contraction magnitude increased exponentially with test-potential.


CONCLUSIONS
The increases in phasic contraction magnitude observed in high-Na cells compared to Na-free cells were most likely due to increased SR Ca loading resulting from increased reverse-mode Na-Ca exchange. Our results also suggest that tonic contractions in high-Na cells were mediated by Ca entry via reverse-mode Na-Ca exchange and were not the result of either SR Ca release or L-type Ca channel activity.
Mattiello
J A
JA
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Margulies
K B
KB
Jeevanandam
V
V
Houser
S R
SR
D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D019831:Sodium-Calcium Exchanger; D019284:Thapsigargin; D012964:Sodium; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium