Muscarinic inhibition of sympathetic C neurones in the bullfrog

Abstract

1. The muscarinic inhibitory post-synaptic potential (i.p.s.p.) in sympathetic C neurones has been characterized in an isolated preparation of bullfrog paravertebral chain ganglia. Interactions between the i.p.s.p. and two other synaptic potentials have also been examined. 2. A single presynaptic stimulus to a C cell produces a nicotinic excitatory post-synaptic potential (e.p.s.p.) followed by a muscarine i.p.s.p. The latency of the i.p.s.p. is 50 msec or longer and the response lasts for seconds. C cells receive multiple cholinergic innervation but the thresholds for activation of the e.p.s.p. and i.p.s.p. are inseparable. Trains of 50 or more presynaptic stimuli produce a non-cholinergic e.p.s.p. which follows the nicotinic e.p.s.p. and i.p.s.p. and which lasts for tens of seconds. 3. The i.p.s.p. produced by a single presynaptic stimulus can be 30 mV in amplitude. However, in most cells, a short train of stimuli applied at an optimal frequency of 10 Hz is required to produce a large i.p.s.p. 4. The i.p.s.p. is blocked by atropine but is not affected by catecholamine antagonists. 5. Ionophoretically applied acetylcholine (ACh) mimics the i.p.s.p. in its latency, time course and amplitude. In addition, the i.p.s.p. and the muscarinic response to ACh reverse polarity at the same membrane potential: -102 mV in normal Ringer solution. The i.p.s.p. reversal potential shifts by 55 mV/decade change in extracellular K+ concentration and is insensitive to the Cl- gradient. 300 microM-Ba2+ totally blocks the muscarinically activated conductance in a reversible manner. 6. Action potentials, when initiated by a supramaximal nicotinic e.p.s.p. or by an antidromic impulse, are not blocked by the i.p.s.p. 7. Near resting potential (-50 to -60 mV), C cells can fire repetitively. The non-cholinergic slow e.p.s.p. is often accompanied by oscillations in membrane potential and firing of action potentials. This repetitive firing of C cells, which appears to be enhanced by the non-cholinergic e.p.s.p., is strongly inhibited by the i.p.s.p. The inhibition can be mimicked by injection of very small hyperpolarizing currents (e.g. 25 pA). Interactions between the i.p.s.p. and the non-cholinergic e.p.s.p. can generate phasic bursting patterns in C cells. 8. The mechanism underlying the i.p.s.p. and the consequences of these findings for ganglionic integration are discussed.