Transitions between repetitive firing and quiescence are observed in excitable cells. The mechanisms that govern such transitions are not fully understood. We postulated that stochastic stimulation with appropriate spectra of amplitudes and frequencies can cause membranes with bistability to switch between repetitive action potentials and quiescence near a steady state, a phenomenon anticipated by models of membrane excitability that exhibit limit cycle behaviour (Paydarfar & Buerkel, 1995; Schneidman et al. 1998).

Membrane potential in squid giant axons was recorded using the intracellular perfusion-axial wire technique as described by Clay & Shlesinger (1983). The extracellular perfusate was filtered seawater, maintained at 10 ± 0.1 °C, and the internal perfusate consisted of 400 mM sucrose and 300 mM potassium glutamate (pH_i 8.5) which is conducive to repetitive firing. Membrane bistability (Guttman et al. 1980) was demonstrated by administering a single brief pulse to initiate repetitive activity from steady state, and by briefly clamping near the equilibrium potential to induce quiescence that persisted after releasing the clamp. Stochastically varying current without offset was administered to the axon for 1-10 s using stimulus profiles that were derived from a model of random (Poisson) inhibitory and excitatory transient potentials with specified amplitude, mean frequency, and time of rise and decay.

In axons with regular repetitive firing, low-level stochastic stimulation rapidly annihilated spontaneous APs, and membrane potential exhibited small subthreshold oscillations near the equilibrium potential. At slightly larger amplitudes of stimulation, irregular single APs or bursts of fairly regular APs alternated with periods of quiescence (Fig. 1). Further increases in the amplitude of stimulation resulted in shorter periods of quiescence. These results were found in all seven axons that exhibited bistability.Stochastic perturbations in membrane potential can cause abrupt and lasting transformations in membrane behaviour, which are related to bistability. Our findings suggest a novel approach to understanding how excitable membranes encode information over long time scales using fast noisy transients.

Figure 1. Repetitive firing intermixed with periods of quiescence during stochastic stimulation (mean 0 µA cm-2).

Clay, J.R. & Shlesinger, M.F. (1983). Biophys. J. 42, 43-53.

Guttman, R., Lewis, S. & Rinzel, J. (1980). J. Physiol. 305, 377-395. abstract

Paydarfar, D. & Buerkel, D.M. (1995). Chaos 5, 18-29.

Schneidman, E., Freedman, B. & Segev, I. (1998). Neural Comput. 10, 1679-1703.