Outflux of various phosphates during membrane depolarization of excitable tissues

Abstract

The main purpose of the present work was to study in detail the outflux of P32 from excitable tissues accompanying membrane depolarization or electrical excitation. With the use of P32 as a tracer, it has been demonstrated that orthophosphate and a number of organic phosphates slowly diffuse out of nerve and muscle even after 2 hr of exposure to Ringer's solution. On exposure to calcium-free or potassium-rich media, or during electrical excitation, there is a considerable increase in the outflux of a number of acid-soluble phosphates, particularly orthophosphate and adenosinetriphosphate. Further evidence in support of this concept was based on the fact that the radioactive specific activity of the diffusible phosphates was greater than the internal phosphates of excitable tissues. Since all these procedures are known to result in depolarization of excitable tissues, there was reason to believe that the outflux of muscle phosphates was somehow related to the physicochemical changes associated with membrane depolarization. The changes in the outflux of P32 from the muscle or nerve, either stimulated or soaked in calcium-free or potassium-rich media, appear to be related to the changes in the membrane potential.

Increase in efflux of inorganic phosphate during electrical activity in small non‐myelinated nerve fibres.

“…Indeed, such an increase has already been reported after long periods of stimulation in myelinated nerve (Mullins, 1954; Abood, Koketsu & Miyamoto, 1962). Unfortunately, in these experiments the collection of the phosphate efflux was not restricted to the region of conducted action potentials, but involved also the region underneath the stimulating electrodes, which may have led to artifactual transmembranal ion fluxes (see Keynes & Ritchie, 1965).…”

Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non‐adrenergic inhibitory nerves in the gut

“…Two lines of argument indicate that the increased nucleoside efflux is not due simply to the release of ATP from nerve membranes, an event which is claimed to occur as any excitable membrane undergoes the permeability changes responsible for the action current (Abood et al, 1962 (Bennett, 1969) (1969) has been unable to find evidence of ATP release from the spleen when the adrenergic nerves are stimulated. He expressed the belief that catecholamine release from neuronal stores is qualitatively different from release of adrenal medullary amines (Douglas, 1968).…”

An Analysis of the Responses of the Isolated Portal Vein of the Rabbit to Electrical Stimulation and to Drugs

“…The transient nature of the non-adrenergic relaxation indicates an efficient inactivation mechanism, but at present we have no means of potentiating or antagonizing the response at the receptor level. Minute amounts of ATP have been shown to be released from nerves on depolarization (Abood, Koketsu & Miyamoto, 1962), and it has also been implicated in the vasodilatation produced by antidromic stimulation in the rabbit ear (Holton, 1959). Release of ATP or a related nucleotide might account for the nonadrenergic relaxation.…”