Previous work has shown that Na,K-ATPase of human erythrocytes can ext
ract free energy from sinusoidal electric fields to pump cations up th
eir respective concentration gradients. Because regularly oscillating
waveform is not a featu re of the transmembrane electric potential of
cells, questions have been raised whether these observed effects are b
iologically relevant. Here we show that a random-telegraph fluctuating
electric field (RTF) consisting of alternating square electric pulses
with random lifetimes can also stimulate the Rb+-pumping mode of the
Na,K-ATPase. The net RTF-stimulated, ouabain-sensitive Rb+ pumping was
monitored with Rb-86(+). The tracer-measured, Rb+ influx exhibited fr
equency and amplitude dependencies that peaked at the mean frequency o
f 1.0 kHz and amplitude of 20 V/cm. At 4 degrees C, the maximal pumpin
g activity under these optimal conditions was 28 Rb+/RBC-hr, which is
approximately 50% higher than that obtained with the sinusoidal electr
ic field. These findings indicate that Na,K-ATPase can recognize an el
ectric signal, either regularly oscillatory or randomly fluctuating, f
or energy coupling, with high fidelity. The use of RTF for activation
also allowed a quantitative theoretical analysis of kinetics of a memb
rane transport model of any complexity according to the theory of elec
troconformational coupling (ECC) by the diagram methods. A four-state
ECC model was shown to produce the amplitude and the frequency windows
of the Rb+-pumping if the free energy of interaction of the transport
er with the membrane potential was to include a nonlinear quadratic te
rm. Kinetic constants for the ECC model have been derived. These resul
ts indicate that the ECC is a plausible mechanism for the recognition
and processing of electric signals by proteins of the cell membrane.