From Perception Threshold to Ion Channels—A Computational Study

Abstract

Small-surface-area electrodes have successfully been used to preferentially activate cutaneous nociceptors, unlike conventional large area-electrodes, which preferentially activate large non-nociceptor fibers. Assessments of the strengthduration relationship, threshold electrotonus, and slowly increasing pulse forms have displayed different perception thresholds between large and small surface electrodes, which may indicate different excitability properties of the activated cutaneous nerves. In this study, the origin of the differences in perception thresholds between the two electrodes was investigated. It was hypothesized that different perception thresholds could be explained by the varying distributions of voltage-gated ion channels and by morphological differences between peripheral nerve endings of small and large fibers. A two-part computational model was developed to study activation of peripheral nerve fibers by different cutaneous electrodes. The first part of the model was a finite-element model, which calculated the extracellular field delivered by the cutaneous electrodes. The second part of the model was a detailed multicompartment model of an Ad-axon as well as an Ab-axon. The axon models included a wide range of voltage-gated ion channels:

Characterization of Inhibitory Effectiveness in Hyperpolarization-Activated Cation Currents by a Group of ent-Kaurane-Type Diterpenoids from Croton tonkinensis

“…Hyperpolarization-activated cation current (I h ) has been recognized as a key determinant of repetitive electrical activity present in heart cells and in a variety of central neurons, and neuroendocrine or endocrine cells [9][10][11][12][13][14][15][16][17]. This current with the slow activation kinetics is a mixed inward Na + /K + current which is sensitive to block by CsCl, ivabradine or zatebradine [18,19], and the increase in this current magnitude can result in depolarizing membrane potential to threshold required for the generation of action potential (AP), thereby influencing pacemaker activity and impulse propagation [10,13,16,20,21]. Correspondingly, the slow kinetics of I h in response to long-step membrane hyperpolarization can also produce long-lasting activity-dependent changes in the excitability of electrically excitable cells [17].…”

“…Sci. 2020,21, 1268 8 of Effect of croton-03 on erg-mediated K + current (IK(erg)) in GH3 cells. In these experiments, cells were bathed in Ca 2+ -free, high-K + solution, and the electrode was filled with K + -containing solution.…”

“…Sci. 2020,21, 1268 9 of Effect of croton-03 on sag potential identified in GH3 cells. Cells were bathed normal Tyrode' solution containing 1.8 mM CaCl2 and 1 μM tetrodotoxin.…”

A test-retest reliability study of assessing small cutaneous fibers by measuring current perception threshold with pin electrodes

“…Transcutaneous electrical stimulation from a constant current stimulator (DS5; Digitimer Ltd; Welwyn Garden City, UK) was applied in the right forearm 7 cm distal to the cubital fossa. The stimulations were applied with an epicutaneous pin electrode consisting of a circular array (diameter: 10 mm) of fifteen cathodal electrodes each with diameter of 0.2 mm, protruding 1 mm from the base, and a large circular stainless steel plate served as an anode with an inner diameter of 20 mm and an outer diameter of 40 mm placed concentrically around the cathodes (Made in Aalborg University, Denmark) ( Fig 1A) [7,9]. The electrode was fixed by a tape after placed on the forearm.…”

“…Previous studies showed that compared to surface patch electrode, the circular pin electrode can preferably active A-δ nerve fibers [6,7]. The Neurometer 1 electrodes also have a relatively larger surface compared to the pin electrodes.…”