1. With the use of a fast-flow system, brief applications (40 ms) of a
cetylcholine on whole cell voltage-clamped dissociated bullfrog sympat
hetic neurons caused an inward current due to the opening of channels
associated with nicotinic acetylcholine receptors. In cells clamped at
- 39 mV, a slower inward current developed after a latency of similar
to 200 ms, owing to M-current inhibition. 2. The second phase of the
response was mediated by the activation of muscarinic receptors and ev
oked by muscarine. 3. The time elapsed from the termination of maximal
agonist application (10 mu M muscarine) to the initiation of recovery
was 4.5 s. This value was independent of the duration of the stimulus
between 0.5 and 10 s. In contrast, applications > 4 a were necessary
to reach 95% of the maximal inhibition during agonist application. 4.
These results have three important implications. 1) The M-current modu
lation rime course does not reflect either the time course of muscarin
ic receptor activation, or the time course of second-messenger product
ion. 2) The latency of M-current inhibition is not due to the distance
between muscarinic acetylcholine receptor (AChR) and nicotinic AChR.
3) Saturating concentrations of the second messenger are produced in <
500 ms in response to maximal concentrations of agonist.