Desensitization of the muscarinic acetylcholine receptor of atrium in bullfrogs.

Abstract

The membrane of bullfrog atrial muscle is hyperpolarized by an increase of K+ conductance in carbachol-containing Ringer solution. The present experiment demonstrated that both the membrane hyperpolarization and K+ conductance increase showed a decay during prolonged application of carbachol, suggesting desensitization of the muscarinic receptor. Such a decay of the membrane conductance increase was also observed when the membrane potential was clamped at the level of the K+ equilibrium potential; no net flow of K+ across the membrane was expected under such a condition. When carbachol was withdrawn from the external solution after its application for 5-10 min, both the membrane potential and conductance quickly returned to normal control values within 3-4 min, suggesting that the ionic distribution across the membrane also returned to normal. Under such a condition, however, the response to a second application of carbachol was depressed for an extended period. Similarly, decay of the response was observed when carbachol was applied repeatedly for a short period with a short time interval. These results suggested that the muscarinic receptor of the present preparation shows desensitization to carbachol. Similar results were obtained with acetylcholine. The rate of onset of desensitization to carbachol was very slow compared with that of the end-plate; the half-time was 6.62 +/- 2.24 min (mean +/- SD, n=13). This rate, however, was dependent on the membrane potential level and the Ca2+ concentration in the external solution, as in the case of the end-plate, suggesting that the molecular mechanism of desensitization occurring at the receptor-ionic channel complex of the muscarinic receptor of the atrial muscle was comparable with that of the nicotinic receptor of the end-plate.