Journal of Neurophysiology, Vol 75, Issue 1 518-521, Copyright © 1996 by APS
Progression of M-current inhibition after agonist removal
A. Villarroel
Department of Neurobiology and Behavior, State University of New York at Stony Brook 11794, USA.
1. With the use of a fast-flow system, brief applications (40 ms) of
acetylcholine on whole cell voltage-clamped dissociated bullfrog
sympathetic 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 approximately 200
ms, owing to M-current inhibition. 2. The second phase of the response was
mediated by the activation of muscarinic receptors and evoked by muscarine.
3. The time elapsed from the termination of maximal agonist application (10
microM 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 s were necessary to reach 95% of the maximal
inhibition during agonist application. 4. These results have three
important implications. 1) The M-current modulation time course does not
reflect either the time course of muscarinic receptor activation, or the
time course of second-messenger production. 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.
