TY - JOUR
T1 - Unitary cardiac Na+,Ca2+ exchange current magnitudes determined from channel-like noise and charge movements of ion transport
AU - Hilgemann, Donald W.
N1 - Funding Information:
I thank L. J. DeFelice, D. C. Gadsby, and C. M. Baud for thoughtful criticism and encouragement; C.-C. Lu and A. Kabakov for discussions and providing cells; S. Feng for technical assistance; R. P. Malchow for helpful comments on the manuscript; and K. D. Philipson and D. A. Nicoll for providing cRNA for NCXl. This work was supported by grants from the National Institutes of Health (5-R1-HL51323-03) and the American Heart Association (95014830).
PY - 1996/8
Y1 - 1996/8
N2 - The cardiac Na+,Ca2+ exchanger (NCX1) is thought to achieve a high turnover rate, but all estimates to date are indirect. Two new strategies demonstrate that maximum unitary exchange currents are about 1 fA (6000 unitary charges per s) and that they fluctuate between on and off levels similar to ion channel currents. First, exchange current noise has been identified in small cardiac patches with properties expected for a gated transport process. Noise power density spectra correlate well with exchanger inactivation kinetics, and the noise has a predicted bell-shaped dependence on the activation state of the exchanger. From the magnitudes of exchange current noise, maximum unitary exchange currents are estimated to be 0.6-1.3 fA. Second, charge movements with rates of ~5000 s-1 have been isolated for the transport of both Na+ and Ca2+ in giant membrane patches using nonsaturating ion concentrations. The Na+ transport reactions are disabled or 'immobilized' by exchanger inactivation reactions, thus confirming that inactivation generates fully inactive exchanger states.
AB - The cardiac Na+,Ca2+ exchanger (NCX1) is thought to achieve a high turnover rate, but all estimates to date are indirect. Two new strategies demonstrate that maximum unitary exchange currents are about 1 fA (6000 unitary charges per s) and that they fluctuate between on and off levels similar to ion channel currents. First, exchange current noise has been identified in small cardiac patches with properties expected for a gated transport process. Noise power density spectra correlate well with exchanger inactivation kinetics, and the noise has a predicted bell-shaped dependence on the activation state of the exchanger. From the magnitudes of exchange current noise, maximum unitary exchange currents are estimated to be 0.6-1.3 fA. Second, charge movements with rates of ~5000 s-1 have been isolated for the transport of both Na+ and Ca2+ in giant membrane patches using nonsaturating ion concentrations. The Na+ transport reactions are disabled or 'immobilized' by exchanger inactivation reactions, thus confirming that inactivation generates fully inactive exchanger states.
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U2 - 10.1016/S0006-3495(96)79275-5
DO - 10.1016/S0006-3495(96)79275-5
M3 - Article
C2 - 8842214
AN - SCOPUS:0029737545
SN - 0006-3495
VL - 71
SP - 759
EP - 768
JO - Biophysical journal
JF - Biophysical journal
IS - 2
ER -