MODEL PREDICTIONS OF IONIC MECHANISMS UNDERLYING BEATING AND BURSTING PACEMAKER CHARACTERISTICS OF MOLLUSCAN NEURONS

The general properties of the excitable membrane in molluscan [Archidoris, Anisodoris, Aplysia and Helix] pacemaker neurons can be described on the basis of experimental evidence available in the literature. The neuronal membrane exhibits under voltage clamp an initial inward current carried by Na+ and Ca2+ ions, the time- and voltage-dependent characteristics of which are similar to that of other excitable structures. The conductance mechanism for the 2 ion species and the transport kinetics appear to be similar. The time course and amplitude of the delayed outward current carried by K+ ions shows a marked dependence on the membrane potential. Characteristic for the molluscan neurons is the existence of an additional fast transient outward current, activated only by hyperpolarizing shifts from the membrane potential. A regular beating discharge over a wide range of frequencies can be predicted by assuming a metabolically controlled driving of the Na+ conductance. Bursting pacemaker characteristics can be correctly simulated by the model if sinusoidal variations of an additional Na+ and Ca2+ conductances gNa and gCa, and periodic variations of the K+ conductance gK, governed by the known operation of a metabolic substrate cycle are introduced. The close approximation of experimentally observed impulse bursts requires that the actual impulse-frequency and the amplitude of the afterspike hyperpolarization are determined by the temporal pattern of gNa, while the spike amplitude is controlled by gCa which (although of similar time course) lags in phase behind gNa. The periodic changes in additional K+ conductance gK, are responsible for burst termination and the changes in interburst interval, to the effect that spike doublets, triplets and multi-spike bursts can be simulated by a suitable choice for the time characteristics of gK. The model makes use of the finding that the Ca2+ inflow associated with a spike discharge actually activates GK, so that large postburst hyperpolarizations can be obtained in high-frequency bursts.