Desensitization in Denervated Mouse Muscles

In denervated mouse soleus (DSOL) muscle preparations washed in Na methanesulfonate solutions containing 30 mmol X 1(-1) K+, bath-applied ACh (55 mumol X 1(-1) ) caused the resting potential to decrease from about -36 to -3.2 mV within 2-4 s; the potential remained stable or became slightly more negative when ACh was applied for 1- 2 min. Two components of the membrane current change (ACh current) were found in DSOL when using a point voltage clamp, an initial current component declining to 1/2 the initial amplitude in 11-15 s (desensitization) and a steady late current comprising 16-47% of the maximum ACh current. Membrane conductance (in microseconds X cm-2) was 0.35 in the absence of ACh, 20.3 at the peak of the initial current, and 1.57 during late current. The late current saturated at 0.55 to 5.5 mumol X 1(-1) ACh, whereas the initial current required 55 or more mumol X 1(-1) ACh to saturate. The null (reversal) potential was 6-13 mV more positive for the late current than for the initial current. The late current was masked when Na+ was replaced by Tris+, sucrose, or K+. An initial and a late current could also be distinguished in non-denervated endplates. The late current was more sensitive to ACh than the initial current, but the null potential was more negative than that for the initial current in endplates. In denervated membrane, the half time of desensitization was increased when Mg2+ was replaced by Ca2+ but the changes were on the average less than 15% the control values. It was concluded that desensitizing and non-desensitizing receptors may exist in extrajunctional membranes of denervated muscles and in endplates, the two being attached to different ionic channels.