THE EFFECT OF pH ON NICOTINE-INDUCED CONTRACTURE AND Ca⁴⁵ MOVEMENTS IN FROG SARTORIUS MUSCLE

¹ Department of Pharmacology, Medical College of Virginia, Richmond, Virginia

The contracture and three-fold increase in Ca⁴⁵ uptake induced by 2.5 mM nicotine in frog sartorius muscle can be inhibited by lowering the pH of the Ringer's bathing solution from 8.4 to 7.4. The nicotine-induced contracture and Ca⁴⁵ efflux obtained at pH 8.4 after prolonged washout in O-Ca-Ringer's solution containing 4 mM EDTA are also inhibited by decreasing the pH to 7.4. If the amount of nicotine in pH 7.4 Ringer's solution is raised to 10 mM, the concentration of nonionized nicotine is approximately equal to that present in pH 8.4 Ringer's solution containing 2.5 mM nicotine. The contracture and increased Ca⁴⁵ uptake induced by 10 mM nicotine in the pH 7.4 Ringer's solution does not differ significantly from that obtained using pH 8.4 Ringer's solution containing 2.5 mM nicotine. The uptake of C¹⁴-labeled nicotine into frog sartorius muscles is more than doubled by increasing the pH of the Ringer's solution from 7.4 to 8.4. These observations indicate that the magnitude of the nicotine-induced contracture and Ca⁴⁵ movements is dependent upon the concentration of nonionized nicotine in the bathing solution. Thus, the nonionized form of nicotine appears to be the molecule of importance not only for penetration of the cell membrane, but for alterations in Ca⁴⁵ movements and contracture tension in frog sartorius muscle.