The effects of sodium ion and rate of stimulation on the refractory period of isolated rabbit atrial muscle.

TEIGER, D., F. ScHEwzR AND A. FARAH: The effects of sodium ion and rate of stimulation on the refractory period of isolated rabbit atrial muscle. J. Pharmac. exp. Ther. 155: 58-68, 1967. Variations in sodium ion concentration and rate of stimulation influence the effective refractory period of rabbit atrial musde. Thus sodium chloride concentrations higher than normal and an increase in rate of stimulation decreased while low NaCl Concentrations and a decrease in rate of stimulation increased the effective refractory period of heart muscle. An increase in potassium ion concentration in the bathing solution increased the effective refractory period of rabbit atrial muscle and this increase could be reversed by addition of NaCl or by an increase in heart rate. Addition of sufficient amounts of quinidine or a decrease in the bath temperature from 37.5#{176}C to about 25#{176}C also increased the refractory period of atrial muscle. NaCl addition or an increase in heart rate could not reverse this increase in the effective refractory period. The results obtained have been discussed in the light of the ionic theory of impulse production. According to the most prevalent theory of impulse production and propagation, depolarization of an excitable membrane is accompanied by a sudden increase in the sodium permeability of the membrane (Hodgkin, 1951; Hodgkin and Huxley, 1952). An increase in the rate of stimulation can decrease the refractory period of cardiac muscle (Dawes and Vane, 1956). This suggests that sodium entry during depolarization may be a factor in the electrical recovery of cardiac muscle. We have thus investigated the effects of varying the extracellular sodium ion concentration and rate of stimulation on the refractory period of rabbit auricular muscle. The addition of quinidine, the elevation of potassium concentration, or a decrease in temperature of the bathing solution (Dawes and Vane, 1956) can increase the effective refractory period (ERP) of cardiac muscle. Bellet et al. (1959a,b), Finch and Marchand (1943) and Cox and West (1961) have shown that sodium Received for publication May 19, 1966. ‘Supported by a grant-in-aid from Sterling Winthrop Research Institute, and the Heart Association of Onondaga County, N.Y. ‘Predoctoral fellow supported by U.S. Public Health Service Training Grant 2G-293(C3). Present address: Sterling Winthrop Research Institute, Rensselaer, N.Y. lactate or sodium chloride can reverse some of the toxic effects of quinidine, potassium chloride or procaine amide on cardiac action potentials. We have thus determined the effects of sodium ion and rate of stimulation on the changes in the effective refractory period produced by quinidine, potassium chloride and temperature changes. METHODS. Albino rabbits weighing 1.5 to 2 kg were sacrificed by a blow on the head and the left atria were rapidly removed and placed in oxygenated Tyrode’s solution’ kept at about 37#{176}C. The left atrium was mounted on a holder containing stimulating and recording electrodes, which was placed in a 50or 100-ml muscle bath containing Tyrode’s solution, kept in a constanttemperature bath at a temperature of 37.5 ± 0.1#{176}C. All solutions used to wash the atria were kept in the same constant-temperature bath as the muscle bath. The left atrium was usually stimulated at a basal rate of 1/sec by means of a Grass stimulator generating square waves of 2or 5-msec duration and a voltage about two times threshold. Test impulses were introduced from a second Grass stimulator which could be ‘The Tyrode’s solution used had the following composition: NaC1, 137 mM; KCI, 2.7 mM; NaH2PO4, 0.41 mM; CaCI,, 1.8 mM; MgCl2, 0.6 mM; NaHCO3, 12 mM; glucose, 5.6 mM.