Effect of age on responsiveness of isolated rat atria to carbachol and on binding characteristics of atrial muscarinic receptors

: Inotropic and chronotropic responses to carbachol were studied in isolated, electrically driven left atria and in spontaneously beating right atria from 6-month-old (adult) and 25-month-old (senescent) rats. The inotropic, but not the chronotropic, response to carbachol was reduced in the senescent animals. However, the inotropic response to nifedipine was not significantly different in the two groups. Likewise, the number (Bmax) and affinities of binding sites for the muscarinic antagonist [3H]quinuclidinyl benzylate (Kd) and for the muscarinic agonist carbachol (Ki) did not change with age. The reduced responsiveness to the inotropic effect of carbachol in senescent animals may result from alteration in events distal to the muscarinic receptor and proximal to Ca2+ transport.