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1. Voltage clamp currents were recorded during iontophoretic application of steady doses of acetylcholine (ACh), carbachol or suberyldicholine to hyperpersensitive extrasynaptic regions of chronically denervated frog muscle fibers. Autocorrelation functions of drug induced current fluctuations were calculated and estimates of conductance gamma and average open time tau of the extrasynaptic ion channels were derived. 2. The average open time of an extrajunctional channel induced by acetylcholine is tauACh = 11 +/- 1-6 msec (+/- S.E.) at -80 mV and 8 degrees C. Carbachol and suberyldicholine open channels of tauCarb = 3-9 +/- 0-4 msec and tauSubCh = 19 +/- 2-5 msec (+/- S.E.) duration under the same conditions. The average open time of the extrasynaptic channel produced by each drug is three to five times longer than the value found for junctional channels in normal fibres. 3. The average open time of the extrajunctional channel is dependent on temperature and membrane potential. Lowering the temperature or increasing the membrane potential increases the average open time of the channels induced by any one of the drugs. 4. The conductance of a single extrajunctional channel opened by the action of acetylcholine is estimated to be gammaextra = 15 +/- 1-8 pmho (+/- S.E.). This is somewhat lower than the value of gammaep = 23 +/- 2 pmho (+/- S.E.) found for the conductance of a single open channel in the junctional membrane of normal fibres. The extrasynaptic channels opened by the action of carbachol and suberyldicholine have similar conductances to those produced by ACh. 5. The autocorrelation function of drug-induced current fluctuations, recorded at the former end-plate region of chronically denervated fibres often shows both a fast and a slow time constant. They correspond in value to the time constant of the autocorrelation function obtained from end-plate currents in normal fibres and from extrasynaptic currents in denervated fibres respectively. This could indicate that two populations of channels exist at the former end-plate region of denervated muscle fibres.

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