Proprioception of all animals is important in being able to have coordinated locomotion. Stretch activated ion channels (SACs) transduce the mechanical force into electrical signals in the proprioceptive sensory endings. The types of SACs vary among sensory neurons in animals as defined by pharmacological, physiological and molecular identification. The chordotonal organs within insects and crustaceans offer a unique ability to investigate proprioceptive function. The effects of the extracellular environment on neuronal activity, as well as the function of associated SACs are easily accessible and viable in minimal saline for ease in experimentation. The effect of extracellular [Ca2+] on membrane properties which affect voltage-sensitivity of ion channels, threshold of action potentials and SACs can be readily addressed in the chordotonal organ in crab limbs. It is of interest to understand how low extracellular [Ca2+] enhances neural activity considering the SACs in the sensory endings could possibly be Ca2+ channels and that all neural activity is blocked with Mn2+. It is suggested that axonal excitability might be affected independent from the SAC activity due to potential presence of calcium activated potassium channels (K(Ca)) and the ability of Ca2+ to block voltage gated Na+ channels in the axons. Separating the role of Ca2+ on the function of the SACs and the excitability of the axons in the nerves associated with chordotonal organs is addressed. These experiments may aid in understanding the mechanisms of neuronal hyperexcitability during hypocalcemia within mammals.
The review surveys various aspects of the plasticity of nerve fibres, in particular the prolonged increase in their excitability evoked by polarization, focusing on a long-lasting increase in the excitability of myelinated afferent fibres traversing the dorsal columns of the spinal cord. We review the evidence that increased axonal excitability (i) follows epidurally applied direct current as well as relatively short (5 or 10 ms) current pulses and synaptically evoked intrinsic field potentials; (ii) critically depends on the polarization of branching regions of afferent fibres at the sites where they bifurcate and give off axon collaterals entering the spinal grey matter in conjunction with actions of extrasynaptic GABAA membrane receptors; and (iii) shares the feature of being activity-independent with the short-lasting effects of polarization of peripheral nerve fibres. A comparison between the polarization evoked sustained increase in the excitability of dorsal column fibres and spinal motoneurons (plateau potentials) indicates the possibility that they are mediated by partly similar membrane channels (including non-inactivating type L Cav++ 1.3 but not Na+ channels) and partly different mechanisms. We finally consider under which conditions trans-spinally applied DC (tsDCS) might reproduce the effects of epidural polarization on dorsal column fibres and the possible advantages of increased excitability of afferent fibres for the rehabilitation of motor and sensory functions after spinal cord injuries.
AbstractAxons reliably conduct action potentials between neurons and/or other targets. Axons have widely variable diameters and can be myelinated or unmyelinated. Although the effect of these factors on propagation speed is well studied, how they constrain axonal resilience to high frequency spiking is incompletely understood. Maximal firing frequencies range from ~ 1 Hz to > 300 Hz across neurons, but the process by which Na/K pumps counteract Na+ influx is slow, and it is unclear the extent to which slow Na+ removal is compatible with high frequency spiking. Modeling the process of Na+ removal in unmyelinated and myelinated axons shows that both increasing diameter and myelination slow down [Na+] accumulation and increase axonal resilience to high frequency spiking. Increasing pump density alleviates [Na+] accumulation, but can paradoxically reduce the resilience. We speculate that [Na+] accumulation may contribute to fatigue after continuous high frequency firing.SignificanceThe reliability of spike propagation in axons is determined by complex interactions between ionic currents, ion pumps and morphological properties. We use compartment-based modeling to uncover that interactions of diameter, myelination and the Na/K pump determine axonal resilience to high frequency spiking. The Na/K pump can play a double-edged sword role in affecting axonal excitability. Our findings suggest that slow sodium removal influences axonal resilience to high frequency spiking, and may also contribute to fatigue.
The Effect of Calcium Ions on Mechanosensation and Neuronal Activity in Proprioceptive Neurons
