Rate of Antagonism of Tubocurarin by Potassium Ions

Abstract

The rate at which potassium ions antagonized the neuromuscular block produced by tubocurarine has been examined in isolated rat diaphragm muscle preparations. The half-time was dependent on the thickness of the muscle. In thick muscles (550 to 650 p) the rate of action could be largely accounted for by the time which the potassium took to diffuse through the interstitial fluid to produce an increase in concentration in the immediate environment of the muscle fibre.It is well known that addition of potassium antagonizes the blocking action of tubocurarine in skeletal muscle (Wilson & Wright, 1936;Quilliam & Taylor, 1947). When this is studied in isolated muscle, the process takes a measurable time for completion, and it was of interest to determine how far diffusion of potassium through the interstitial spaces to its site of action could account for the time relations. METHODSThe solution bathing the diaphragm was similar to that used by Creese (1954) except that the potassium content was reduced to 1.5 mm. The fluid was bubbled with a mixture of 5% carbon dioxide and 95% oxygen, and the temperature of the bath was maintained at 380 C.The left hemi-diaphragm from an albino rat weighing 100 to 150 g was removed, attached to a holder and immersed in the solution in such a manner that single maximal shocks could be delivered alternately to the nerve and muscle, using the procedure described by Holmes, Jenden & Taylor (1951) except that condenser shocks of 0.02 /F were used for the nerve and 2 /OF for the muscle. The responses were recorded on smoked paper using a spring-loaded lever. Stimulation was continued throughout the experiments, and the magnitude of the responses obtained by direct and indirect stimulation was very similar. As direct stimulation was almost unaffected by tubocurarine, an estimate of the degree of block could be made at any time during the experiment.The muscle was later removed from the bath, outlined on squared paper and weighed. The thickness was calculated, taking the specific gravity as 1.055 (Creese, 1954) and expressing the result to the nearest S a. RESULTSThe height of contraction of the muscle after immersion in the solution containing 1.5 mm potassium showed an initial decline. The solution was changed repeatedly until the height of contraction became steady, usually after 2 hr.

Communications

“…the node of Ranvier (Stampfli, 1959) or the muscle of a superfused frog ventricle (Lamb & McGuigan, 1966) the resulting depolarization is rapid in onset. As the intertransverse muscle of our preparation (Gladden & Kidd, 1969) is only slightly thicker than the rat diaphragm, the penetration of which by K+ is also rapid (Creese, Taylor & Tilton, 1961), it seems improbable that diffusion, even to the middle of the muscle where the spindles are situated (Gladden, 1969) Assuming that recovery of neuromuscular transmission indicates that K+ has reached an effective depolarizing concentration throughout the muscle slip (Creese et al 1961), we must conclude that the time taken for the diffusion of the K+ cannot explain, on its own, the latency of the spindle excitation. It is possible that an intermediate process is involved, and the feasibility of this being an intramuscular excitation of sympathetic fibres by the elevated K+ concentration is being studied.…”