Biomaterial Database

The voltage dependence of I(h) in human myelinated axons. 2012

James Howells, and Louise Trevillion, and Hugh Bostock, and David Burke

Institute of Clinical Neurosciences, Royal Prince Alfred Hospital and The University of Sydney, Sydney, Australia. james.howells@sydney.edu.au

HCN channels are responsible for I(h), a voltage-gated inwardly rectifying current activated by hyperpolarization. This current appears to be more active in human sensory axons than motor and may play a role in the determination of threshold. Differences in I(h) are likely to be responsible for the high variability in accommodation to hyperpolarization seen in different subjects. The aim of this study was to characterise this current in human axons, both motor and sensory. Recordings of multiple axonal excitability properties were performed in 10 subjects, with a focus on the changes in threshold evoked by longer and stronger hyperpolarizing currents than normally studied. The findings confirm that accommodation to hyperpolarization is greater in sensory than motor axons in all subjects, but the variability between subjects was greater than the modality difference. An existing model of motor axons was modified to take into account the behaviour seen with longer and stronger hyperpolarization, and a mathematical model of human sensory axons was developed based on the data collected. The differences in behaviour of sensory and motor axons and the differences between different subjects are best explained by modulation of the voltage dependence, along with a modest increase of expression of the underlying conductance of I(h). Accommodation to hyperpolarization for the mean sensory data is fitted well with a value of -94.2 mV for the mid-point of activation (V(0.5)) of I(h) as compared to -107.3 mV for the mean motor data. The variation in response to hyperpolarization between subjects is accounted for by varying this parameter for each modality (sensory: -89.2 to -104.2 mV; motor -87.3 to -127.3 mV). These voltage differences are within the range that has been described for physiological modulation of I(h) function. The presence of slowly activated I(h) isoforms on both motor and sensory axons was suggested by modelling a large internodal leak current and a masking of the Na(+)/K(+)-ATPase pump activity by a tonic depolarization. In addition to an increased activation of I(h), the modelling suggests that in sensory axons the nodal slow K(+) conductance is reduced, with consequent depolarization of resting membrane potential, and action potential of shorter duration.

UI	MeSH Term	Description	Entries
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008959	Models, Neurological	Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Neurologic Models,Model, Neurological,Neurologic Model,Neurological Model,Neurological Models,Model, Neurologic,Models, Neurologic
D009046	Motor Neurons	Neurons which activate MUSCLE CELLS.	Neurons, Motor,Alpha Motorneurons,Motoneurons,Motor Neurons, Alpha,Neurons, Alpha Motor,Alpha Motor Neuron,Alpha Motor Neurons,Alpha Motorneuron,Motoneuron,Motor Neuron,Motor Neuron, Alpha,Motorneuron, Alpha,Motorneurons, Alpha,Neuron, Alpha Motor,Neuron, Motor
D009186	Myelin Sheath	The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.	Myelin,Myelin Sheaths,Sheath, Myelin,Sheaths, Myelin
D011984	Sensory Receptor Cells	Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.	Nerve Endings, Sensory,Neurons, Sensory,Neuroreceptors,Receptors, Neural,Neural Receptors,Receptors, Sensory,Sensory Neurons,Sensory Receptors,Nerve Ending, Sensory,Neural Receptor,Neuron, Sensory,Neuroreceptor,Receptor Cell, Sensory,Receptor Cells, Sensory,Receptor, Neural,Receptor, Sensory,Sensory Nerve Ending,Sensory Nerve Endings,Sensory Neuron,Sensory Receptor,Sensory Receptor Cell
D004558	Electric Stimulation	Use of electric potential or currents to elicit biological responses.	Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D001369	Axons	Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.	Axon
D015221	Potassium Channels	Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.	Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel