POSTNATAL DECREASE IN CHRONOTROPIC SENSITIVITY TO ACETYLCHOLINE IN RAT-HEART

1. The negative chronotropic effects of acetylcholine and carbachol on isolated rat right atria were examined at 0, 4, 8 and 16 weeks after birth. 2. Acetylcholine produced negative chronotropic responses at al l ages and completely abolished spontaneous beating at its maximum eff ective concentration. 3. The sensitivity to acetylcholine, expressed i n terms of ED(50) values, was higher at 0 and 4 weeks than at 8 and 16 weeks, ED(50) values (mu M) at 0, 4, 8 and 16 weeks being 9.5 +/- 1.8 (n = 12), 13.2 +/- 3.4(n = 11), 59.3 +/- 10.9 (n = 14) and 51.5 +/- 1 7.5 (n = 5), respectively. 4. Neostigmine produced a leftward shift of the concentration-response curve for acetylcholine both at 4 and 8 we eks after birth. The shift was larger at 8 weeks and no difference in sensitivity to acetylcholine was observed between the two ages in the presence of neostigmine. 5. Further, no developmental changes were obs erved in the sensitivity to carbachol, which is not hydrolyzed by chol inesterase. 6. We concluded that the chronotropic sensitivity to acety lcholine of rat atria decreases post-natally during the period between 4 and 8 weeks after birth due to increase in cholinesterase activity.