Abstract
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 states 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 approximately 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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