6533b855fe1ef96bd12affcf

RESEARCH PRODUCT

Model predictions of the ionic mechanisms underlying the beating and bursting pacemaker characteristics of molluscan neurons

subject

description

The general properties of the excitable membrane on molluscan pacemaker neurons can be described on the basis of a fair amount of experimental evidence available in the literature. The neuronal membrane exhibits under voltage clamp an initial inward current carried by both 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 two ion species and the transport kinetics appear to be closely 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 which is only activated by hyperpolarizing shifts from the membrane potential. A regular beating discharge over a wide range of frequencies can be predicted by making the assumption of 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 ?g Na and ?g Ca, and periodic variations of the K+ conductance ?g K, governed by the known operation of a metabolic substrate cycle are introduced. The close approximation of experimentally observed impulse bursts requires that the actual inpulse-frequency and the amplitude of the after-spike hyperpolarization are determined by the temporal pattern of ?g Na, while the spike amplitude is controlled by ?g Na which (although of similar time course) is lagging in phase behing ?g Na. The periodic changes in additional K+ conductance ?g K, are responsible for burst termination and the changes in inter-burst interval, to the effect that spike doublets, triplets and multi-spike bursts can be simulated by a suitable choice for the time characteristics of ?g K. The model makes use of the finding that the Ca2+ inflow associated with a spike discharge actually activates ?g K, so that large postburst hyperpolarizations can be obtained in high-frequency bursts.