RECOGNITION AND PROCESSING OF RANDOMLY FLUCTUATING ELECTRIC SIGNALS BY NA,K-ATPASE

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.