© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Contribution of reverse-mode sodium–calcium exchange to contractions in failing human left ventricular myocytes
aDepartment of Physiology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA
bDepartment of Cardiology, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140, USA
cDepartment of Cardiothoracic Surgery, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140, USA
* Corresponding author. Tel. (+1-215) 707-3278; Fax (+1-215) 707-4003; E-mail: srhouser@astro.ocis.temple.edu
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 µmol/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.
KEYWORDS Calcium influx; Contraction; Excitation-contraction coupling; Heart ventricle; Human myocyte; Sarcoplasmic reticulum; Sodium–calcium exchange
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