Role of the time dependence of Boltzmann open probability in voltage-gated proton channels

Abstract

The modeling and simulation of experimental families of current-time (I-t) curves of dimeric voltage-gated proton channels and of proton-conducting voltage sensing domains (VSDs) with a minimum of free parameters requires the movement of protons to be controlled by the rate of increase of the Boltzmann open probability p over time in passing from the holding to the depolarizing potential. Families of I-t curves of protomers and proton-conducting VSDs can be satisfactorily fitted by the use of a single free parameter expressing the rate constant kp for the increase of p over time. Families of I-t curves of dimeric Hv1 channels can be fitted by a model that assumes an initial proton current I1 flowing along the two monomeric units, while they are still operating separately; I1 is gradually replaced by a slower and more potential-dependent current I2 flowing when the two monomers start operating jointly under the control of the coiled-coil domain. Here too, p is assumed to increase over time with a rate constant kp that doubles in passing from I1 to I2, with fit requiring three free parameters. Chord conductance yields erroneously high gating charges when fitted by the Boltzmann function, differently from slope conductance.