Delayed onset and slow time course of the non-M-type muscarinic current in bullfrog sympathetic neurons

Abstract

The onset and time course of the muscarinic currents induced by brief applications of acetylcholine (ACh) were examined in voltage-clamped neurons of bullfrog sympathetic ganglia bathed in a solution containing d-tubocurarine. At a potential of -40 mV, the ACh-induced current (IACh) appeared within 1.2 s and rapidly increased to its peak with a half-activation time of 2.2 s. This initial current was termed the fast IACh and was blocked by 4 mM Ba2+. At a potential more negative than -60 mV, the fast IACh disappeared and the remaining IACh activated with a delay of 3.9 s and slowly increased to its peak with a half-activation time of 8.2 s. This delayed current was termed the slow IACh and is thought to be associated with inhibition of a K+ current, or IM, as well as activation of an inward current through non-M-type muscarinic cation channels. The slow IACh was not inhibited by Ba2+, but its amplitude was reduced with depolarization (the extrapolated reversal potential was +3 mV). In Na(+)-free solution, the amplitude of the slow IACh reduced, but its polarity did not reverse in the voltage region examined (-30 to -100 mV). The slow excitatory postsynaptic current was also recorded, and was shown to have a similar delay in onset and slow time course. The results demonstrate that ACh activates the non-M-type muscarinic current three times more slowly than it inhibits IM.