ASYMMETRICAL BLOCKADE OF POTASSIUM EXCHANGE IN MUSCLE BY SKF 525-A: COMPARISON WITH BUTACAINE

¹ Department of Pharmacology, University of Connecticut, Schools of Medicine and Dental Medicine, Farmington, Connecticut

-Diethylaminoethyl diphenylpropylacetate hydrochloride (SKF 525-A) and its analogs, -dimethylaminoethyl (SKF 484-A) and -aminoethyl (SKF 26754-A) (5-10 x 10^-5 M) caused a blockade of ⁴²K exchange in resting frog striated muscle which was not modified in Na⁺- or Cl^--free solutions and was not affected by strophanthidin. The blockade was asymmetrical, in that ⁴²K efflux was inhibited to a greater extent than was ⁴²K uptake, but there was no net accumulation of [K⁺]₁. Prolonged equilibration with SKF 525-A had no effect on the asymmetry of the blockade. Unlike SKF 525-A, the local anesthetics, butacaine (1-50 x 10^-5 M) and procaine (5-10 x 10^-4 M) blocked ⁴²K uptake and efflux symmetrically. The inhibition of ⁴²K efflux, caused by SKF 525-A and local anesthetics, was not overcome by elevation of [K⁺]₀ from 5 to 25 mM. Elevation of [H⁺]₀ reduced the blockade of ⁴²K exchange caused by either SKF 525-A (pK_a 5.7) or butacaine (pK_a 8.9), but not that caused by benzocaine (pK_a 3.2: 1 x 10^-3 M). In 2.5 mM [K⁺]0 Cl^--free solutions SKF 525-A and butacaine (5-10 x 10^-5 M) caused a 5 to 10 mV depolarization of the resting membrane potential.