Endothelin causes prolonged inhibition of nicotinic transmission in feline colonic parasympathetic ganglia.
The action of endothelin (0.03-1 microM) on neurons in colonic parasympathetic ganglia of cats was studied in vitro, using intracellular microelectrode recording techniques. Electrical stimulation of the pelvic nerve evoked excitatory postsynaptic potentials (EPSPs) and orthodromic action potentials that were reversibly blocked by (+)-tubocurarine, hexamethonium, or external solutions containing nominal zero calcium and elevated magnesium. Endothelin blocked orthodromic action potentials and caused a concentration-dependent prolonged reversible depression of fast EPSPs. Endothelin had minimal effects on nicotinic depolarizations evoked by pressure application of acetylcholine. Endothelin also caused membrane depolarization (2-12 mV) followed by membrane hyperpolarization (1-8 mV). The depolarization and hyperpolarization were associated with a decrease and increase in membrane input resistance, respectively. The actions of endothelin were not altered by superfusion of the ganglia with external solutions containing atropine (300 nM), yohimbine (300 nM), naloxone (1 microM), or substance P (3 microM). We conclude that endothelin modulates synaptic transmission by slow membrane depolarization, membrane hyperpolarization, and prolonged depression of fast EPSPs. We suggest that the blockade of orthodromic action potentials and the depression of fast EPSPs is primarily due to inhibition of release of acetylcholine from presynaptic terminals.
Nishimura
T
T
Department of Physiology, Michigan State University, East Lansing 48824.
Krier
J
J
Akasu
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003106:Colon / Q000294:innervation*; D004553:Electric Conductivity; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D005726:Ganglia, Parasympathetic / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D009433:Neural Inhibition; D009538:Nicotine / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D016232:Endothelins; D009538:Nicotine; D000109:Acetylcholine