Sensitivity of membranes to their environment. Role of stochastic processes

Ionic flow through biomembranes often exhibits a sensitivity to the environment, which is difficult to explain by classical theory, that usually assumes that the free energy available to change the membrane permeability results from the environmental change acting directly on the permeability control mechanism. This implies, for example, that a change delta V in the trans-membrane potential can produce a maximum free energy change, delta V X q, on a gate (control mechanism) carrying a charge q. The analysis presented here shows that when stochastic fluctuations are considered, under suitable conditions (gate cycle times rapid compared with the field relaxation time within a channel), the change in free energy is limited, not by the magnitude of the stimulus, but by the electrochemical potential difference across the membrane, which may be very much greater. Conformational channel gates probably relax more slowly than the field within the channel; this would preclude appreciable direct amplification of the stimulus. It is shown, however, that the effect of impermeable cations such as Ca++ is to restore the amplification of the stimulus through its interaction with the electric field. The analysis predicts that the effect of Ca++ should be primarily to affect the number of channels that are open, while only slightly affecting the conductivity of an open channel.