Nerve excitability changes in chronic renal failure indicate membrane depolarization due to hyperkalaemia

Abstract

Multiple nerve excitability measurements were used to investigate axonal membrane properties in patients with chronic renal failure (CRF). Nine patients were studied during routine haemodialysis therapy. The median nerve was stimulated at the wrist and compound muscle action potentials recorded from abductor pollicis brevis. Stimulus-response behaviour, strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle (refractoriness, superexcitability and late subexcitability) were recorded using a recently described protocol. In six patients, sequential studies were performed before, during and after haemodialysis. All patients underwent standard electrolyte and renal function tests before and after haemodialysis. Before dialysis, there were significant abnormalities in axonal excitability: reduced superexcitability; increased accommodation to depolarizing and hyperpolarizing currents; and a steeper current-threshold relationship compared with normal controls. These excitability parameters are the most sensitive to membrane potential and the abnormalities, which were all reduced by haemodialysis, closely resembled those in normal axons depolarized by ischaemia. Before dialysis, the excitability parameters correlated significantly with serum potassium (range 4.3-6.1 mM), but not with other markers of renal dysfunction: patients with normal axonal resting potentials had normal serum potassium, although urea and creatinine were elevated. We conclude that nerves are depolarized in many CRF patients and that the depolarization is primarily due to hyperkalaemia.

Silencing the Kir4.1 Potassium Channel Subunit in Satellite Glial Cells of the Rat Trigeminal Ganglion Results in Pain-Like Behavior in the Absence of Nerve Injury

“…Conventional models of neuronal ion balance predict that a disruption of the ability of SGCs to maintain normal levels of extracellular K ϩ would be associated with altered excitability of primary sensory neurons (Laming et al, 2000;Walz, 2000) and would thus lead to abnormal sensory perception. In support of this model, hyperkalemia, direct K ϩ injection, or inhibition of K ϩ uptake all lead to neuronal hyperexcitability (Traynelis and Dingledine, 1988;Janigro et al, 1997;Kiernan et al, 2002).…”

Association Between Calcineurin Inhibitor Treatment and Peripheral Nerve Dysfunction in Renal Transplant Recipients

“…Multiple excitability parameters were recorded using previously published protocols (10,14,15). These parameters included threshold electrotonus and current threshold recordings which utilize subthreshold electrical stimuli to provide information on nerve membrane potential and internodal conductances (16).…”

Velocity recovery cycles of human muscle action potentials and their sensitivity to ischemia

“…5,17,22,24 Excitability measurements, such as peak increase in excitability after a conditioning impulse (superexcitability), are particularly sensitive to changes in membrane potential. Excitability studies have provided evidence that membrane depolarization is involved in the pathophysiology of axonal neuropathies such as uremic neuropathy 18,20 and critical illness polyneuropathy, 28 and these findings have important implications for treatment. 20,21 We considered it highly desirable to develop a comparable method for the indirect estimation of membrane potential changes in muscle.…”