Effects of substance P on neurones of the inferior mesenteric ganglia of the guinea‐pig

Abstract

The membrane effects of substance P on neurons of isolated inferior mesenteric ganglia and the underlying ionic mechanisms were investigated by intracellular recording techniques. When applied to the neurons by superfusion, substance P (0.5 .mu.M) caused a membrane depolarization; in a few neurons, the depolarization was preceded by a small hyperpolarization. Substance P effects were not altered in a low Ca2+/high Mg2+ solution or in a solution containing D-tubocurarine and atropine. When the membrane potential was clamped manually at the resting level between -50 and -60 mV, substance P caused, in about an equal number of neurons, a slight to moderate decrease and also increase of membrane resistance; a brief increase occurred prior to the decrease of membrane resistance. In neurons with high resting membrane potential (> -70 mV), substance P elicited a large depolarization accompanied by a marked increase in membrane resistance; the latter was probably due to anomalous rectification. Conditioning hyperpolarization of the membrane close to the level of EK [K equilibrium potential] increased and decreased substance P-induced depolarization in 11 and 2 neurons, respectively. Substitution of external Na+ with an equimolar amount of either sucrose or Tris buffer markedly attenuated the depolarizing effect of substance P. The substance P-induced depolarization was diminished in a high K+ (10 mM) solution, and it could be augmented when membrane was hyperpolarized to EK. The effect of substance P was not appreciably affected in a low Cl- solution. Substance P depolarizes the sympathetic neurons by increasing and decreasing membrane permeability to Na+ and K+, respectively, and that the concomitant membrane resistance change depends on interaction of GNa [Na conductance] activation and GK inactivation. Substance P may possibly be the transmitter mediating the non-cholinergic slow excitatory potential elicited by repetitive preganglionic stimulation in the neurons of the inferior mesenteric ganglia.