AJP - Cell Physiology, Vol 264, Issue 2 C342-C351, Copyright © 1993 by American Physiological Society
Desensitization and reactivation of ACh-regulated exocrine secretion in hen tracheal epithelium
B. Winding and N. Bindslev
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
We have studied acetylcholine (ACh) desensitization of Cl- secretion and
its reactivation by atropine in the hen tracheal epithelium employing
voltage-clamp technique. Adding 4 microM ACh to the serosal side induces a
maximal bumetanide-sensitive Cl- secretion. The ACh-induced Cl- secretion
is desensitized nearly 100% at 512 microM ACh. The desensitization of Cl-
secretion may be reduced 30-40% by 0.32 microM atropine (reactivation).
From a kinetic model for desensitization and reactivation with two
muscarinic receptors (mAChR), we have estimated the maximal secretory
response, the apparent dissociation coefficients, and the apparent Hill
coefficients for ACh and atropine at the two receptors. Based on the
kinetic model we can predict an optimal fixed concentration ratio (Ofcor)
between ACh and atropine that will maintain Cl- secretion above 40% of
maximum over a wide concentration range, ACh 1-4,100 microM, and we have
confirmed the predicted Ofcor experimentally. A cellular model is proposed
with two mAChR, one stimulatory and another inhibitory, that accounts for
an observed dissociation between desensitization in short-circuit current
and conductance.
