Potassium and the excitability properties of normal human motor axons in vivo.

Hyperkalemia is an important cause of membrane depolarization in renal failure. A recent theoretical model of axonal excitability explains the effects of potassium on threshold electrotonus, but predicts changes in superexcitability in the opposite direction to those observed. To resolve this contradiction we assessed the relationship between serum potassium and motor axon excitability properties in 38 volunteers with normal potassium levels. Most threshold electrotonus measures were strongly correlated with potassium, and superexcitability decreased at higher potassium levels (P = 0.016), contrary to the existing model. Improved modelling of potassium effects was achieved by making the potassium currents obey the constant-field theory, and by making the potassium permeabilities proportional to external potassium, as has been observed in vitro. This new model also accounted well for the changes in superexcitability and other excitability measures previously reported in renal failure. These results demonstrate the importance of taking potassium levels into account when assessing axonal membrane dysfunction by excitability testing, and provide evidence that potassium currents are activated by external potassium in vivo

Multiple excitability measurements recorded from normal subjects: motor axons in the median nerve were tested at the wrist and compound muscle action potentials recorded from the abductor pollicis brevis muscle.

<p>A–C: Mean +/− SD for all 38 subjects. D–F: Comparisons between means of Lower K (grey) and Higher K (black) groups. A, D: Threshold electrotonus, <i>i.e.</i>, threshold changes during and after polarizing currents set to +40 (top), +20, −20 and −40% (bottom) of threshold. B, E: Recovery cycle showing successive phases of refractoriness, superexcitability, and late subexcitability. C,F: Current-threshold (I/V) relationship.</p

Potassium dependence of 2 nerve excitability measurements predicted by Models 1 (red line), 2 (green line) and 3 (blue line) compared with mean measurements for Higher K (▴), Medium K (•) and Lower K (▪) groups, and ellipse representing 1 SD limits for 9 patients with chronic renal failure (reproduced from Kiernan et al.).⁹

<p>Only Model 3 predicts an appropriate drop in superexcitability with increasing potassium level.</p

Mean values of excitability parameters derived from the multiple measures of nerve excitability performed on the median nerve in 38 normal subjects.

<p>First column shows mean ± standard deviation (SD). Second column shows Pearson product moment correlation coefficient between excitability measure and serum potassium. Third column shows p values (* = P<0.05, ** = <i>P</i><0.01, *** = <i>P</i><0.001). SDTC: strength-duration time constant. TEd20 and TEh20: threshold electrotonus changes due to depolarizing and hyperpolarizing currents respectively, set to 20% of control threshold; TEd40, TEh40 same, but for 40% polarizing currents; expressions in square brackets indicate times after start of 100 ms current, early [10–20 ms], late [90–100 ms] or around peak threshold change [ peak]. I/V: current-threshold. RRP: relative refractory period.</p

Threshold electrotonus (top row) and recovery cycle (bottom row) waveforms generated by Models 1–3 for values of extracellular potassium corresponding to the Lower K (grey) and Higher K (black) groups.

<p>Threshold electrotonus (top row) and recovery cycle (bottom row) waveforms generated by Models 1–3 for values of extracellular potassium corresponding to the Lower K (grey) and Higher K (black) groups.</p

Examples of nerve excitability measures showing significant relationship to serum potassium levels.

<p><b>A</b>: Superexcitability, <b>B</b>: TEd20(90–100 ms) threshold decrease at end of 20% depolarizing current, <b>C,D</b>: TEh20(90–100 ms) and TEh40(90–100 ms) threshold decrease at end of 20% and 40% hyperpolarizing current (NB Negative threshold decrease indicates threshold were increased by hyperpolarization).</p

Comparison between the three models in their ability to account for the effects of changes in serum potassium levels on multiple measures of nerve excitability.

<p>Data from Medium K data was fitted to nerve model, and then adjusted for different potassium levels according to Models 1, 2 and 3. Discrepancies score difference between model and recorded data and discrepancy reductions score improvement over no allowance for potassium. For each data set Model 3 provides lowest discrepancy (figures in bold).</p