On the electrogenic sodium pump in mammalian non‐myelinated nerve fibres and its activation by various external cations

Abstract

SUMMARY1. A study has been made of the hyperpolarization that follows a period of electrical activity (the post-tetanic hyperpolarization) in mammalian non-myelinated nerve fibres.2. Evidence is presented that under certain circumstances this posttetanic hyperpolarization is a result of activity of an electrogenic sodium pump that normally is absolutely dependent on the external presence of potassium.3. When the external chloride is replaced by sulphate or by isethionate the post-tetanic hyperpolarization, which in normal Locke solution is only a few millivolts in amplitude, is increased usually to about 20 mV, and on occasion to 35 mV.4. This effect of removing the chloride takes several minutes to develop and is consistent with the idea that the increase in the post-tetanic response is the result of removing the short-circuiting effect of internal chloride ions (by their being washed out into the chloride-free bathing medium).5. Small anions, such as chloride, nitrate, iodide, bromide, and thiocyanate can short-circuit the electrogenic pump, whereas larger anions such as sulphate and isethionate cannot. The bicarbonate ion, which is larger than chloride, short-circuits the pump but less effectively.6. In Locke solution containing 5 mm potassium the post-tetanic hyperpolarization declines exponentially, with a time constant of about 1-3 min. The time constant is inversely related to the external potassium concentration.7. However, when the external potassium concentration is zero the hyperpolarization declines rapidly to a very small value. Subsequent * Present address: Department of Pharmacology, University of Oxford.H. P. RANG AND J. M. RITCHIE addition of potassium to the bathing medium causes a marked redevelopment of the hyperpolarization.8. This potassium-activated response declines exponentially with a time constant that is inversely related to the potassium concentration. When the added potassium concentration is 5 mm, the time constant is 1-9 min.9. The amplitude of the potassium-activated response increases with increasing concentrations of potassium.10. Other cations can produce this activated response. Thus, thallium is more effective than, rubidium as effective as, caesium and ammonium about 1/10 as effective as, and lithium ions about 1/30 as effective as potassium in producing the activated response. Choline is quite ineffective.11. The size of the post-tetanic response is little affected by changes in the duration of the period of stimulation. However, increasing the duration definitely increases the time constant of recovery.12. Reducing the external sodium concentration increases the size of the post-tetanic hyperpolarization (by about 25 %), but the effect is complex and requires further study. 13. Reducing the calcium of the Locke-solution from 2-2 to 0-2 mm has no appreciable effect on the post-tetanic response, nor has increasing the pH of the Locke from 7-2 to 9-2.14. When the membrane potential is increased or decreased, by externally applied currents, there is relatively little change i...

The electrogenic Na‐pump and spontaneous contraction of the hypokalemic rat duodenum

“…The peak post-tetanic hyperpolarization of non-myelinated nerve fibres of the rabbit was also found to decline significantly at a [Kb. exceeding 2 mM (Rang & Ritchie, 1968), and the peak hyperpolarization of 'Na-loaded' taenia coli of guinea-pig diminished and disappeared more rapidly with increasing [Kbo (Casteels et al, 1971). These results are consistent with the present findings, in which the period of reduced tone of 'Na-rich' duodenum with the addition of K4 became shorter when increasing [K]b from 0.5 to 120mM.…”

Activity‐dependent slowing of conduction differentiates functional subtypes of C fibres innervating human skin

“…However, although K¤ conductances are well known to modulate axonal excitability (Bostock et al 1998), there is, as yet, no evidence that they can cause sufficient hyperpolarization to block conduction. In the case of repetitively stimulated rabbit vagus C fibres in vitro, increasing extracellular K¤ actually increases the hyperpolarization, due to activation of the sodium pump (Rang & Ritchie, 1968). Whatever the mechanisms involved, the variations in activity-dependent slowing have important functional implications.…”

Genetic dissection of short-term and long-term facilitation at the Drosophila neuromuscular junction.

“…After 30 min, single nerve stimuli produced the large, slow ejps, and many spontaneous ejps were seen, presumably caused by a depolarization of the nerve terminal. For the mutant in a medium containing 0.14 mM Ca2+, 64 mM Li+, and 64 mM Na+, within 15 Increasing the external K+ concentration accelerates sodium pump activity in mammalian nonmyelinated nerve fibers (28). If this applies to Drosophila, there should be less accumulation of internal Na+ in a high K+ medium.…”