KINETIC-ANALYSIS OF CAMP-ACTIVATED NA+ CURRENT IN THE MOLLUSCAN NEURON - A DIFFUSION REACTION MODEL

cAMP-activated Na+ current (I(Na,cAMP)) was studied in voltage-clamped neurons of the seaslug Pleurobranchaea californica. The current response to injected cAMP varied in both time course and amplitude as the tip of an intracellular injection electrode was moved from the periphery to the center of the neuron soma. The latency from injection to peak response was dependent on the amount of cAMP injected unless the electrode was centered within the cell. Decay of the I(Na,cAMP) response was slowed by phosphodiesterase inhibition. These observations suggest that the kinetics of the I(Na,cAMP) response are governed by cAMP diffusion and degradation. Phosphodiesterase inhibition induced a persistent inward current. At lower concentrations of inhibitor, I(Na,cAMP) response amplitude increased as expected for decreased hydrolysis rate of injected cAMP. Higher inhibitor concentrations decreased I(Na,cAMP) response amplitude, suggesting that inhibitor-induced increase in native cAMP increased basal I(Na,cAMP) and thus caused partial saturation of the current. The Hill coefficient estimated from the plot of injected cAMP to I(Na,cAMP) response amplitude was close to 1.0. An equation modeling I(Na,cAMP) incorporated terms for diffusion and degradation. In it, the first-order rate constant of phosphodiesterase activity was taken as the rate constant of the exponential decay of the I(Na,cAMP) response. The stoichiometry of I(Na,cAMP) activation was inferred from the Hill coefficient as 1 cAMP/channel. The equation closely fitted the I(Na,cAMP) response and simulated changes in the waveform of the response induced by phosphodiesterase inhibition. With modifications to accommodate asymmetric I(Na,cAMP) activation, the equation also simulated effects of eccentric electrode position. The simple reaction-diffusion model of the kinetics of I(Na,cAMP) may provide a useful conceptual framework within which to investigate the modulation of I(Na,cAMP) by neuromodulators, intracellular regulatory factors, and pharmacological agents.