The interaction of ionic currents mediating single spike activity in retinal amacrine cells of the tiger salamander.

We investigated the ionic interactions responsible for the characteristic nonrepetitive spike activity of amacrine cells. First we measured 4 pharmacologically separable ionic components: a voltage-gated, transient inward sodium current, a voltage-gated, sustained inward calcium current, a calcium-gated, sustained outward potassium current, and a voltage-gated, transient outward potassium current. The measurements provided the time course and magnitudes of the underlying conductances as functions of voltage. Each current was simulated following conventional Hodgkin-Huxley theory. A composite of the simulated currents was analytically reassembled to generate an approximation of the voltage response to a current step. By artificially varying the magnitude and kinetics of the different conductances in the simulation, we determined the range of values that supported the nonrepetitive spike-like response. Amacrine cells tend to remain refractory following an initial spike because (1) the entire activation range for potassium is located at positive potentials with respect to sodium inactivation, so sodium inactivation is never fully extinguished, and (2) the fully activated sodium conductance is of insufficient magnitude to subsequently reach threshold, given this residual inactivation. Shifting the sodium inactivation range by 10 mV, or increasing sodium conductance by 5 times, leads to a more repetitive form of activity. Changes in the magnitude, time course, or activation range of the potassium conductance cannot alter these conditions.