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. 2006 Dec;53(12 Pt 1):2445-54.
doi: 10.1109/TBME.2006.884640.

Mechanism of Nerve Conduction Block Induced by High-Frequency Biphasic Electrical Currents

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Free PMC article

Mechanism of Nerve Conduction Block Induced by High-Frequency Biphasic Electrical Currents

Xu Zhang et al. IEEE Trans Biomed Eng. .
Free PMC article

Abstract

The mechanisms of nerve conduction block induced by high-frequency biphasic electrical currents were investigated using a lumped circuit model of the myelinated axon based on Frankenhaeuser-Huxley (FH) model or Chiu-Ritchie-Rogart-Stagg-Sweeney (CRRSS) model. The FH model revealed that the constant activation of potassium channels at the node under the block electrode, rather than inactivation of sodium channels, is the likely mechanism underlying conduction block of myelinated axons induced by high-frequency biphasic stimulation. However, the CRRSS model revealed a different blocking mechanism where the complete inactivation of sodium channels at the nodes next to the block electrode caused the nerve conduction block. The stimulation frequencies to observe conduction block in FH model agree with the observations from animal experiments (greater than 6 kHz), but much higher frequencies are required in CRRSS model (greater than 15 kHz). This frequency difference indicated that the constant activation of potassium channels might be the underlying mechanism of conduction block observed in animal experiments. Using the FH model, this study also showed that the axons could recover from conduction block within 1 ms after termination of the blocking stimulation, which also agrees very well with the animal experiments where nerve block could be reversed immediately once the blocking stimulation was removed. This simulation study, which revealed two possible mechanisms of nerve conduction block in myelinated axons induced by high-frequency biphasic stimulation, can guide future animal experiments as well as optimize stimulation waveforms for electrical nerve block in clinical applications.

Figures

Fig. 1
Fig. 1
Axon model to simulate conduction block induced by high-frequency biphasic electrical currents. The inter-node length Δx = 100d; d is the axon diameter. L is the nodal length. Each node is modeled by a resistance-capacity circuit based on FH or CRRSS model. Ra: axoplasm resistance; Rm: membrane resistance; Cm: membrane capacitance; Va: intracellular potential; Ve: extracellular potential; Single pulse: 0.5-2 mA intensity, 0.1 ms pulse width; High-frequency pulses: 0-10 mA intensity, 1-20 kHz for FH model, 1-40 kHz for CRRSS model.
Fig.2
Fig.2
Method to test the axon recovery from conduction block. The time delay (D) between the application of the test pulse and the stop of block stimulation was varied in different tests, so that the action potential evoked by the test pulse could arrive at the block electrode at a time when the axon recovery was at a different stage.
Fig.3
Fig.3
Conduction block simulated by FH model in (a) and (b), and by CRRSS model in (c) and (d). Axon diameter: 10 μm. Stimulation in (a) and (b): 8 kHz, 1.2 mA. The blocking threshold is 1 mA at 8 kHz for FH model. Stimulation in (c) and (d): 30 kHz, 0.7 mA. The blocking threshold is 0.65 mA at 30 kHz for CRRSS model.
Fig.4
Fig.4
FH Model: propagation of membrane potentials, ionic currents, and activation/inactivation of the ion channels near the block electrode when nerve conduction block occurs as shown in Fig.3 (a) and (b). The legends in (e) indicate the distances of each node to the block electrode (node at 0.0 mm is under the block electrode). m – activation of Na+ channels; h – inactivation of Na+ channels; n – activation of K+ channels.
Fig.5
Fig.5
CRRSS Model: propagation of membrane potentials, ionic/leakage currents, and activation/inactivation of the ion channels near the block electrode when nerve conduction block occurs as shown in Fig.3 (c) and (d). The legends in (e) indicate the distances of each node to the block electrode (node at 0.0 mm is under the block electrode). m – activation of Na+ channels; h – inactivation of Na+ channels.
Fig.6
Fig.6
Change of membrane potential, ionic currents, and activation/inactivation of the ion channels after the initial action potential as shown in Fig.3 at the node (0.0 mm) under the block electrode in FH model: (a) and (b); or at the node (1.0 mm) next to the block electrode in CRRSS model: (c) and (d). The stimulation waveform is re-scaled and plotted on the background to show the timing. m – activation of Na+ channels; h – inactivation of Na+ channels; n – activation of K+ channels.
Fig.7
Fig.7
Change of membrane potential, ionic currents, and activation/inactivation of the ion channels after the termination of block stimulation at the node (0.0 mm) under the block electrode in FH model. Data from axons of diameter 5 μm and 20 μm are both plotted in this figure for comparison. m – activation of Na+ channels; h – inactivation of Na+ channels; n – activation of K+ channels. Stimulation: 10 kHz, 1.2 mA for 5 μm axon, but 0.41 mA for 20 μm axon. The arrows on the time axis marked the time when block stimulation is terminated.
Fig.8
Fig.8
Recovery from conduction block in FH model. (a). Propagation of action potentials in axons of different diameters are either delayed or blocked when the block stimulation is terminated at a different time [with a different delay (D) relative to the test pulse (see Fig.2)]. (b). Propagation delay of action potential changes with termination delay (D) of the block stimulation. Stimulation: 10 kHz, 1.2 mA.

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